mwwXaiv lus
Tsev / Kev paub / Ntsiab lus

Kev paub

Interleukins, Chemokines, Thiab Tumor Necrosis Factor Superfamily Ligands nyob rau hauv Pathogenesis ntawm West Nile Virus Kab Mob

Sep 08, 2023

Abstract: Tus kab mob West Nile (WNV) yog kab mob yoov tshaj cum uas tuaj yeem ua rau mob encephalitis thiab tuag hauv cov neeg muaj mob. Cytokines ua lub luag haujlwm tseem ceeb hauv kev mob thiab kev tiv thaiv kab mob hauv kev teb rau WNV kab mob. Murine qauv muab pov thawj tias qee cov cytokines muaj kev tiv thaiv kab mob WNV mob hnyav thiab pab nrog kev tshem tawm cov kab mob, thaum lwm tus ua lub luag haujlwm ntau yam hauv WNV neuropathogenesis thiab kev puas tsuaj ntawm cov ntaub so ntswg tiv thaiv kab mob. Kab lus no yog lub hom phiaj los muab cov kev tshuaj xyuas tshiab ntawm cytokine qhia cov qauv hauv tib neeg thiab cov tsiaj sim ua qauv ntawm WNV kab mob. Ntawm no, peb piav qhia txog cov interleukins, chemokines, thiab qog necrosis yam tseem ceeb superfamily ligands cuam tshuam nrog WNV kab mob thiab pathogenesis thiab piav qhia txog lub luag haujlwm nyuaj uas lawv ua hauv kev kho ob qho tib si kev tiv thaiv thiab kab mob ntawm lub hauv nruab nrab paj hlwb thaum lub sij hawm lossis tom qab tshem tawm tus kab mob. Los ntawm kev nkag siab txog lub luag haujlwm ntawm cov cytokines thaum lub sij hawm WNV neuroinvasive kab mob, peb tuaj yeem tsim cov kev kho mob tsom rau kev hloov kho cov kab mob tiv thaiv kab mob kom txo tau cov kab mob neuroinflammation thiab txhim kho cov txiaj ntsig ntawm tus neeg mob.

Ntsiab lus: West Nile tus kab mob; cytokines; interleukins; tshuaj chemokines; qog necrosis yam superfamily ligands; tus qauv kab mob

effects of cistance-antitumor

Suav tshuaj ntsuab cistanche cog-Antitumor

1. Taw qhia

Tus kab mob West Nile (WNV) yog ib qho zoo-sensitive, ib leeg-stranded RNA tus kab mob teej tug mus rau Japanese encephalitis serocomplex, genus Flavivirus, tsev neeg Flaviviridae [1]. Nws lub neej voj voog feem ntau suav nrog cov noog thiab yoov tshaj cum, thaum tib neeg, nees, thiab lwm yam vertebrates raug suav hais tias yog xwm txheej [2]. Lub WNV genome tau muab txhais ua ib qho polypeptide thiab co- thiab post-translationally ua tiav rau hauv kaum proteins: peb cov qauv (capsid C, membrane precursor prM, thiab hnab ntawv E), uas tsim cov virion; xya nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, 2K, NS4B, thiab NS5) koom nrog cov kab mob sib kis, evasion ntawm tus tswv tsev tiv thaiv kab mob, thiab WNV pathogenesis [3]; thiab ib tug peptide 2K, uas plays lub luag hauj lwm nyob rau hauv rearranging cytoplasmic membranes thiab Golgi lag luam ntawm NS4A protein [4]. Qhov cuam tshuam rau WNV yog qhov sib txawv ntawm nws cov tswv [5]. Feem ntau ntawm WNV kab mob hauv tib neeg yog asymptomatic lossis mob me, tshwm sim nrog mob taub hau, tsis muaj zog, thiab / lossis kub cev [6]. Txawm li cas los xij, ib feem me me ntawm cov neeg mob WNV (tsawg dua 1% [7]) yuav tsim cov kab mob neuroinvasive, suav nrog meningitis, encephalitis, lossis mob tuag tes tuag taw, rau leej twg tuag tshwm sim hauv 10-30% ntawm cov neeg mob [8,9] . Lub sij hawm ntev lub cev thiab kev paub txog kev noj qab haus huv, suav nrog kev qaug zog, qaug zog, myalgia, nco lossis hnov ​​​​lus tsis hnov ​​​​lus, kev nyuaj siab, thiab lub cev tsis muaj zog, kuj tuaj yeem tshwm sim hauv 30 txog 60% ntawm cov neeg mob uas muaj kab mob kho mob [9-11]. Txawm hais tias tam sim no suav tias yog tus kab mob zoonotic tseem ceeb tshaj plaws rau Asmeskas cov pej xeem [12], tsis muaj cov txheej txheem kho mob sab nraud ntawm kev txhawb nqa, thiab tsis muaj cov tshuaj FDA pom zoo lossis tshuaj tiv thaiv muaj rau kev kho lossis tiv thaiv kab mob WNV neuroinvasive, raws li [8]. WNV pathogenesis yog tus cwj pwm los ntawm peb theem: (1) lub sijhawm ntxov ntawm daim tawv nqaij kis kab mob thiab kis mus rau cov qog ntshav hauv zos tom qab raug yoov tshaj cum tom, (2) kis kab mob mus rau cov kab mob peripheral, thiab (3) ntxeem tau ntawm lub hauv paus. paj hlwb (CNS) [13]. Txhawm rau tawm tsam qhov ntxeem tau ntawm WNV, tus tswv tsev tsiaj txhu tau npaj peb kab ntawm kev tiv thaiv: daim tawv nqaij thiab lub cev tiv thaiv kab mob hauv lub cev thaum ntxov tom qab los ntawm kev hloov pauv (humoral thiab cellular) tiv thaiv tom qab theem [13,14]. Cytokines yog cov cim qhia cov protein uas tau nthuav tawm los ntawm ntau lub cev tiv thaiv kab mob thiab cov kab mob nonimmune mammalian hlwb (Daim duab 1). Lawv induction thiab kev tswj xyuas nruj txuas nrog WNV replication thaum lub sij hawm thaum ntxov ntawm tus kab mob [15–20]. Thaum lawv koom nrog txhua peb kab ntawm kev tiv thaiv WNV, lawv kuj ua rau lub cev tiv thaiv kab mob hauv lub hlwb puas. Ntawm cov cytokines no, interleukins (ILs), chemokines, thiab qog necrosis factor superfamily (TNFSF) ligands yog cov tseem ceeb hauv kev tiv thaiv WNV, raws li pov thawj los ntawm transcriptome profiling ntawm WNV-mob hlwb thiab cov ntaub so ntswg siv DNA microarrays los yog RNA sequencing [21]. Ntau qhov kev tshuaj xyuas tau pom lawv lub luag haujlwm hauv cov kab mob flaviviral feem ntau [22–24] thiab hauv cov kab mob flaviviral tshwj xeeb, suav nrog dengue [25,26] thiab Zika [27] kab mob. Kev sib raug zoo ntawm flaviviruses elicit txawv immunomodulation profiles nyob rau hauv lawv cov tswv [28–30] thiab sib txawv antagonize antiviral txoj kev [31]; Txawm li cas los xij, WNV pathogenesis zoo li muaj qhov tshwj xeeb piv nrog lwm cov kab mob neurotropic [28,32], uas yuav tau tham thoob plaws hauv qhov kev tshuaj xyuas no. Yog li ntawd, nws yog ib qho tseem ceeb los hais txog lub luag haujlwm ntawm cytokines hauv cov ntsiab lus tshwj xeeb ntawm WNV kab mob.

Figure 1

Daim duab 1. Cellular hom phiaj ntawm tus kab mob West Nile thiab coj cytokine teb nyob rau hauv cov tsiaj. Cov duab kos tau tsim hauv Biorender.com. Cov ntawv luv: BAFF: B-cell activating factor; FasL: Fas ligand; TNF-: qog necrosis factor - , TRAIL: TNF-related apoptosis-inducing ligand.

Muaj cov pov thawj txuas ntxiv uas tus tswv tsev tiv thaiv kab mob, uas tau tsav los ntawm cytokines, ua lub luag haujlwm tseem ceeb hauv kev tsim cov kab mob WNV thiab qhov tshwm sim ntawm tus kab mob. Ua ntej, cov ntaub ntawv kho mob txhawb nqa ntau yam cytokine profiles, nyob ntawm seb poj niam txiv neej [33], kev noj qab haus huv [34], thiab tib neeg polymorphisms hauv cov kab mob tiv thaiv kab mob no [35–37] cuam tshuam nrog cov txiaj ntsig sib txawv ntawm tus kab mob, yog li inciting siv. ntawm biomarkers cuam tshuam los kwv yees qhov hnyav ntawm WNV kab mob hauv qhov chaw kho mob [33]. Qhov thib ob, siv cytokines ua agonists lossis thaiv lawv cov teebmeem los ntawm kev siv tshuaj lossis tshuaj caj ces hauv cov qauv murine tau pom tias lawv muaj peev xwm hloov pauv WNV-txoj kab mob phenotypes [16,38–49]. Yog li ntawd, kev nkag siab zoo dua ntawm kev koom tes ntawm cytokines hauv pathogenesis ntawm WNV tuaj yeem tsis tsuas yog pab txhim kho kev kuaj mob thiab kev kuaj mob xwb tab sis kuj qhia kev tshawb fawb txog kev tiv thaiv kab mob tiv thaiv kab mob los kho WNV-vim cov kab mob neurological. Hauv kev tshuaj xyuas no, peb sau cov kev tshawb pom los ntawm kev tshawb fawb soj ntsuam nrog rau cov kev sim ua dhau los ob xyoo dhau los siv hauv vitro thiab hauv vivo WNV tus kab mob qauv kom rov ua dua ILs, chemokines, thiab TNFSF ligands uas koom nrog WNV kab mob, qhia cov paub txog qhov cuam tshuam hauv WNV pathogenesis, thiab txheeb xyuas cov neeg sib tw xav tau kev tshawb fawb ntxiv kom paub txog lawv qhov kev cuam tshuam raws li cov hom phiaj kho mob.

Benefits of cistanche tubulosa-Antitumor

Cov txiaj ntsig ntawm cistanche tubulosa-Antitumor

2. Interleukins (ILs) hauv WNV Kab Mob

ILs yog cov proteins uas hloov pauv kev loj hlob ntawm tes, sib txawv, thiab ua kom muaj zog thaum cov tshuaj tiv thaiv kab mob [50]. WNV induces tso tawm tsawg kawg 22 ILs nyob rau hauv mammalian hosts (Table S1). Txog hnub tim, IL-1, IL-6, IL-10, IL-12, IL-17A, IL-22, thiab IL{{ 9}} tau raug tshawb xyuas ncaj qha (Table 1), thaum muaj cov ntaub ntawv me me txog cov ILs ntxiv uas cuam tshuam rau lub cev tiv thaiv kab mob rau WNV. Table 1. Cov ntsiab lus ntawm interleukins, chemokines, chemokine receptors, thiab qog necrosis factor ligands tshwm sim tom qab tus kab mob West Nile (WNV) kab mob, uas nws pathogenesis tau kawm nyob rau hauv nas qauv hauv vivo.

1694144471368

1694144497060

2.1. Interleukin-1 Tsev Neeg

Tam sim no, 11 cytokines raug suav hais tias yog cov tswv cuab ntawm IL-1 tsev neeg: IL-1 , IL-1 , IL-1 receptor antagonist [IL-1ra], IL-18, IL-33, IL-36 , IL-36 , IL-36 , IL-36ra, IL-37, thiab IL-38 [113,114]. Ntawm lawv, IL-1 [19,76,87,115], IL-1 [10,16,51–53,80,94,116], IL-1ra [16,29,77] ], IL-18 [117], thiab IL-33 [118] paub tias raug tso tawm los teb rau WNV tus kab mob.

IL-1 yog ib qho cytokine muaj zog heev, tshwm sim los teb rau WNV tus kab mob ob qho tib si hauv vitro thiab hauv vivo, nyob rau hauv periphery thiab CNS (Table S1). Lub luag haujlwm ntawm IL-1 hauv WNV tus kab mob tau kawm los ntawm murine qauv tsis muaj IL-1R1 thiab tsis tuaj yeem teb rau IL-1 , IL-1 , lossis IL{ {7}}ra [16,54,66,115]. IL-1R1 signaling conferred tiv thaiv nas tiv thaiv WNV kab mob thiab kev tuag [16]. Thaum ntxov WNV encephalitis, IL-1R1 tswj cov kab mob sib kis thiab tom qab apoptosis hauv cov neurons [16,115]. Tsis tas li ntawd, IL -1 tswj cov leukocyte infiltration nrog rau T cell teb nyob rau hauv CNS [54,66,115] thiab tiv thaiv o los ntawm downregulating pro-inflammatory cytokines, xws li TNF- thiab IL-6 [16] thiab chemokines, xws li CCL2 thiab CCL5 [16,51,54]. Kev txhaj tshuaj Intracranial ntawm WNV hauv cov tsiaj qus-hom C57BL/6 nas coj mus rau qhov tshwm sim tsis zoo txog qhov cuam tshuam ncaj qha ntawm IL-1 ntawm cov kab mob sib kis hauv lub hlwb. Thaum IL-1 tsis tau cuam tshuam ncaj qha rau tus kab mob sib kis hauv CNS hauv qee qhov kev tshawb fawb [51,53,115], IL-1 tau pom los kho CNS-tus kab mob hauv qhov kev txwv hauv lwm txoj kev tshawb fawb [16]. Qhov tsis sib xws ntawm cov kev tshawb fawb no txawm tias siv tib tus qauv ntawm kev kis kab mob tuaj yeem yog ib feem piav qhia los ntawm qhov sib txawv ntawm cov kab mob sib kis tau siv los kis rau nas. Cov pro-inflammatory IL-1 thiab anti-inflammatory IL-1ra cytokine qhia qauv thiab lub luag hauj lwm thaum lub sij hawm tus kab mob WNV tseem tsis meej. Hauv tib neeg sera, IL-1ra qhia tau hloov pauv hauv WNV-tus kab mob presymptomatic thiab asymptomatic pub dawb [29], tab sis upregu lated thaum mob WNV mob [16,34]. Txawm hais tias tsis muaj tib neeg txoj kev tshawb fawb tseem tsis tau tshaj tawm IL-1 kev cai thaum lub sij hawm WNV kab mob, IL-1 kev hloov kho thaum lub sij hawm WNV kab mob sib txawv nyob rau hauv cov kev tshawb fawb siv cov qauv kev sim (Table S1). IL-1 yog ib qho tseem ceeb hauv kev ua rau ntxov, mob, thiab hnyav WNV kab mob. Tseeb tiag, IL-1 yog ib qho ntawm cov cytokines ntxov tshaj plaws uas kuaj pom tom qab muaj yoov tshaj cum tom hauv murine qauv [22,62,119]. Tsis tas li ntawd, qhov no cytokine-mediated epidermal dendritic cell (DC) thiab Langerhans cell migration ntawm lub epidermis mus rau hauv lub zos ntws cov qog ntshav [22,62,119]. Hauv nas hlwb, IL-1 tau zais thaum lub sijhawm mob hnyav, feem ntau yog los ntawm kev nkag mus / cov neeg nyob hauv macrophages [54,63], thiab txawm tias tom qab ntawd thaum rov qab los, feem ntau yog los ntawm astrocytes [63]. Cov pov thawj tam sim no qhia tau hais tias IL-1 ua lub luag haujlwm ob lub sijhawm thaum WNV-induced kab mob, tiv thaiv thaum lub sij hawm mob hnyav, thiab tsav tsheb neurological sequela nyob rau hauv lub sij hawm ntev. Cov nas tsis muaj peev xwm nyob rau hauv ob qho tib si IL-1 signaling thiab Apoptosis-associated speck-zoo li cov protein uas muaj C-terminal caspase recruitment domain (ASC), uas induces caspase-1-nyob rau hauv-inflammasome activation thiab IL{{76} } ntau lawm, tau pom tias nce WNV kab mob titers thiab kab mob hnyav tshwj xeeb hauv CNS [16,51]. Tsis tas li ntawd, hauv tib neeg uas muaj keeb kwm ntawm asymptomatic lossis WNV kab mob hnyav, txo qis IL-1 induction nyob rau hauv lawv cov peripheral ntshav mononuclear hlwb thiab macrophages yog ib qho cim ntawm tus kab mob hnyav [94]. Hauv cov neeg pub ntshav uas kuaj pom qhov zoo rau WNV RNA tom qab kuaj ntshav niaj hnub, IL-1 tau hloov kho hauv cov ntshav rau rau lub hlis tom qab lawv pib pub ntshav thiab sib cuam tshuam nrog WNV RNA loads [16]. Hauv cov nas, xws li kev txhawb nqa IL-1 overexpression, induced tshwj xeeb los ntawm NOD-zoo li receptor-pyrin-muaj proteins 3 (NLRP3) inflammasome cleavage hauv astrocytes tom qab lub sij hawm rov qab los ntawm WNV encephalitis [16,22,63,119], ua rau muaj kev puas tsuaj spatial kev kawm thiab synaptic rov qab [53,63]. Yog li, kev ua tsis zoo NLRP3 inflammasome activation thiab IL-1 zais cia hauv lub hlwb tam sim no suav hais tias yog ib txoj hauv kev zoo rau kev txhim kho lub paj hlwb mus sij hawm ntev tom qab WNV kab mob [120]. IL-18 kuj yog ib qho pro-inflammatory cytokine uas tsim tom qab inflammasome activation [121,122]. WNV kab mob ntawm tib neeg thawj monocyte-derived DCs lossis hloov pauv tib neeg neuroblastoma cell kab (SK-N-SH, ATCC HTB-11™) tsis tau nce IL{107}} ntau lawm [52,117]. Txawm li cas los xij, IL-18 tau raug kho nyob rau hauv cov nqaij mos thiab lub ntsws ntawm WNV-mob nas [76]. IL-18 raug qhia kom ntxiv immunopathogenesis ntawm DENV [123], tab sis tseem tsis tau muaj kev tshawb nrhiav los sim qhov no thaum lub sij hawm kis kab mob WNV. Lwm tus tswv cuab ntawm IL{115}} tsev neeg, IL-33, tau raug kho nyob rau hauv splenic macrophages ntawm WNV-mob nas [118]. IL-33 kev taw qhia los ntawm ST2 receptor tuaj yeem ua rau cov lus teb rau pro-inflammatory thiab anti-inflammatory [124,125]. Feem ntau, hauv kev kis kab mob, IL{125}} suav tias yog tus neeg sawv cev tiv thaiv los ntawm kev txhim kho CD8+ T cell teb [126] thiab txo qis tus kab mob encephalitis los ntawm kev txo qis iNOS qhia hauv CNS [127].

Yog li, nrog rau qhov kev nkag siab no, kev txhawb nqa kev ua haujlwm lossis kev tsim cov cytokine no thaum WNV kis tau tuaj yeem nthuav qhia cov txiaj ntsig kho mob. Kev ua haujlwm ntxiv yog xav tau los tshawb xyuas cov haujlwm ntawm cov cytokine no hauv cov ntsiab lus ntawm WNV kab mob.

Superman herbs cistanche—Anti-inflammatory

Superman tshuaj ntsuab cistanche-Anti-mob

2.2. Interleukin 6 Tsev Neeg

IL-6 yog pleiotropic cytokine koom nrog ntau cov txheej txheem lom neeg, suav nrog kev tiv thaiv kab mob, hematopoiesis, pob txha metabolism, thiab kev loj hlob embryonic [128]. Nws yog ib qho tseem ceeb tshaj plaws cytokines thaum kis kab mob [129], thiab kev tshawb fawb siv cov qauv kev sim sib txawv piav qhia txog IL-6 kev hloov pauv thaum kis WNV (Table S1). Tib neeg cytokine kev tshawb fawb tom qab WNV kis tau zoo heev qhia lub luag haujlwm tseem ceeb rau IL-6. Kev kis mob hnyav hauv tib neeg tuaj yeem ua rau muaj kev sib txuas siab ntawm IL-6 hauv CSF [130] thiab cov ntshav ntshav [130,131] ntawm cov neeg mob uas muaj WNV kub taub hau thiab WNV neuroinvasive kab mob. Ntxiv mus, hauv lwm txoj kev tshawb fawb, IL-6 qib hauv cov ntshav tau qis dua hauv cov neeg noj qab haus huv viremic piv rau cov neeg tsis muaj kab mob ua ntej thiab tom qab IgM seroconversion [124]. IL-6 ntev-hais lus tau tshaj tawm hauv cov ntshav ntawm cov tib neeg uas muaj kev qaug zog ntev ntev tom qab cov tsos mob WNV tus kab mob [132]; Txawm li cas los xij, tseem tsis tau muaj kev tshawb fawb los txhawb txoj kev sib raug zoo ntawm IL-6 qib thiab WNV-kev cuam tshuam tus kab mob hnyav rau tib neeg. Ib qho kev tshawb fawb hauv vivo tau tshawb xyuas qhov kev koom tes ntawm IL-6 hauv WNV tus kab mob [67] thiab tau piav qhia tias, thaum kis tus kab mob WNV, IL-6-cov nas uas tsis muaj peev xwm ua rau pom cov neeg tuag zoo li cov nas qus [67] . Kev ua haujlwm ntxiv yog xav tau los qhia meej seb qhov no yog vim muaj lub luag haujlwm me me ntawm cov cytokine hauv WNV kab mob lossis rau cov kev sim tshwj xeeb uas siv hauv txoj kev tshawb no

2.3. Interleukin 17 Tsev Neeg

Tam sim no, 6 cytokines inflammatory cytokines sawv cev rau IL-17 tsev neeg, uas yog IL-17A, IL-17B, IL-17C, IL-17D, IL{ {6}}E, thiab IL-17F [133]. Ntawm cov no, IL-17A, pro-inflammatory cytokine, yog upregulated hauv vitro [43] thiab hauv vivo [43,76,85] tom qab WNV kab mob (Table S1). Hauv tib neeg, thaum tsis muaj tsos mob, nce IL{16}} qib tau pom nyob rau hauv cov neeg muaj tus kab mob WNV thaum piv rau qib los ntawm cov neeg tsis muaj ntshav pub ntshav [29]. Ntawm qhov tsis sib xws, qib qis heev ntawm IL-17A, nrog rau qhov tsis muaj tiav ntawm IL-17Ib qho kev qhia hauv CSF [130], tau pom nyob rau hauv ob qho tib si febrile thiab neuroinvasive cov neeg mob. Hauv plaub tus neeg mob uas tau lees paub WNV uas muaj cov tsos mob tshwm sim tsis tu ncua, tsis muaj qhov nce hauv IL{24}} tuaj yeem kuaj pom [125]. Cov kev tshawb pom no, qhia txog kev sib txuas ntawm IL-17Ib qho kev qhia thiab qhov txiaj ntsig zoo ntawm WNV tib neeg kev kis tus kab mob, tau txais kev txhawb nqa los ntawm ib qho hauv vivo txoj kev tshawb fawb hauv cov nas, qhov uas lawv pom tias IL-17Kev txhawb nqa WNV tshem tawm los ntawm inducing qhia txog cytotoxic mediator noob thiab txhawb CD{28}} T cell cytotoxicity [43].

2.4. Interleukin 12 Tsev Neeg

IL-12 tsev neeg suav nrog plaub tus tswv cuab: IL-12, IL-23, IL-27, thiab IL-35 [134], ntawm cov IL{{6 }} thiab IL-23 raug tswj hwm hauv vivo tom qab WNV kab mob (Table S1). IL-12 yog tsim los ntawm ob qhov sib txuas sib txuas subunits, p40 thiab p35, uas tsim thaum ua ke nrog bioactive IL-12p70 [134]. IL-23 kuj muaj ob lub subunits, p19 thiab p40, thiab tom kawg tau muab faib rau IL{18}} [134]. Tam sim no, tsis muaj kev tshawb fawb tib neeg tau hais txog IL-23 kev hloov pauv tom qab tus kab mob WNV, tab sis IL-12 tau tshaj tawm tias tau nthuav tawm ntau hauv cov neeg mob ntshav qab zib thiab asymptomatic WNV-mob mob [29] thiab tsis hloov pauv hauv cov tsos mob WNV-mob. cov ntshav pub ntshav thaum ntxov ntawm tus kab mob [34]. Cytokine soj ntsuam hauv cov neeg muaj tus kab mob WNV tau lees paub tias IL-12p70 tuaj yeem tshaj tawm hauv cov ntshav rau lub hlis [132] thiab txawm tias xyoo [135] tom qab kis kab mob. Cov nas uas tsis muaj peev xwm nyob rau hauv ib lub subunits ntawm IL-12 (p35) IL-23 (p19) lossis cov p40 subunit tau siv los txiav txim lub luag haujlwm tshwj xeeb ntawm txhua cytokine. Tsiaj txhu tsis muaj nyob hauv IL-12p40 lossis IL-23p19, tab sis tsis yog IL-12p35, tau txo qis leukocyte homeing rau lub hlwb thiab nce kev tuag, txhawb qhov tseem ceeb ntawm IL-23 nyob rau hauv kev tiv thaiv kab mob ntawm tes infiltration thiab homeing thaum lub sij hawm tus mob theem ntawm tus kab mob [82].

Kev tshawb fawb ntxiv tau lees paub los pov lub teeb ntawm kev koom tes ntawm cov cytokines thaum lub sij hawm rov qab los ntawm WNV kab mob.

2.5. Interleukin 10 Tsev Neeg

IL-10 tsev neeg ntawm cytokines muaj IL-10, IL-19, IL-20, IL-22, IL-24, IL{{6 } }, IL-28, thiab IL-29 [114], ntawm cov uas IL-10 thiab IL{11}} kev qhia yog upregulated nyob rau hauv cov qauv ntawm WNV kab mob (Table S1). Kev nce qib ntawm IL-10 tau kuaj pom nyob rau hauv cov ntshav plasma mob, viremic [124], asymptomatic cov ntshav pub ntshav kuaj tau nrog WNV [29]. Txawm li cas los xij, tsis muaj qhov sib txawv tseem ceeb hauv IL-10 hauv cov ntshav ntshav [130,131] thiab CSF [130] kuaj los ntawm cov neeg mob uas muaj WNV kub taub hau thiab WNV neuroinvasive kab mob tau pom [130]. Genetic los yog pharmacologic blockade ntawm IL-10 kev taw qhia tau pab kom muaj sia nyob tom qab WNV kev sib tw tuag rau cov nas [79], thiab cov kev tshawb fawb ntxiv qhia txog lub luag haujlwm pathogenic ntawm IL-10 nyob rau hauv mob WNV mob. Ua ntej, yav dhau los rhiab heev rau salivary proteins xa los ntawm ntau yam A. aegypti tom ua rau muaj kev nce IL -10 qhia cuam tshuam nrog tus kab mob hnyav [136]. Thib ob, hauv cov nas uas kis tus kab mob hamster-derived WNV, qhov txo qis IL-10 ntau lawm cuam tshuam nrog tsawg zaus ntawm tus kab mob nyob rau hauv tus po piv rau WNV NY99-mob nas [78]. Tsuas yog txoj kev tshawb nrhiav IL-22 tau piav qhia txog qhov cuam tshuam tsawg kawg hauv ib puag ncig, tab sis cov nas tsis muaj nyob hauv IL-22 tau tiv taus ntau dua rau tus kab mob WNV tuag, thiab IL-22 txhawb nqa kev nkag mus thaum ntxov ntawm tus kab mob. - nqa neutrophils rau hauv CNS los ntawm kev tswj cov tshuaj chemotaxis (tsuas yog ntawm Cxcr2 signaling) ntawm cov ntshav-hlwb barrier (BBB) ​​[42].

3. Chemokines hauv WNV Kab Mob

Chemokines yog chemotactic cytokines uas khi rau G protein-coupled receptors kom ncaj qha cell txav thaum homeostasis thiab mob [114]. Cov proteins no tau muab faib ua plaub pawg: C chemokine, CC chemokine, CXC chemokine, thiab CX3C chemokine, raws li tus naj npawb thiab qhov chaw ntawm kev txuag N-terminal cysteine ​​residues [114]. Kev hloov pauv hauv kev qhia ntawm chemokines thiab lawv cov receptors tau pom nyob rau hauv cov lus teb rau WNV kab mob hauv cov qauv tsiaj (Table S2). Cov kev tshawb fawb tsom mus rau chemokines receptors, suav nrog Ccr2, Ccr5, Ccr7, Cxcr2, Cxcr3, Cxcr4, thiab Cx3cr1 hauv WNV-tus qauv tau pab txhais qhov tseem ceeb ntawm cov tshuaj chemokines hauv lub sijhawm- thiab lub cev tshwj xeeb (Table 1). Txawm li cas los xij, txhua tus ntawm cov receptors no tuaj yeem raug khi rau ntau cov tshuaj chemokines, thiab ob peb tsab ntawv ceeb toom txog kev koom tes ntawm chemokines hauv WNV kab mob muaj nyob rau niaj hnub no, suav nrog CCL2, CCL7, thiab CXCL10 (Table 1). Yog li, qhov tseem ceeb ntawm tus neeg chemokines thaum kis WNV xav tau kev tshawb fawb ntxiv.

3.1. CC Chemokines

3.1.1. CCL2, CCL7 thiab CCL12 (Ccr2 Agonists)

Ccr2 thiab nws cov ligands ua lub luag haujlwm tseem ceeb hauv monocyte mobilization nyob rau hauv cov mob inflammatory [137], thiab lawv tuaj yeem raug ntxias tom qab kev sim WNV kab mob (Table S2). Ccr2 agonist CCL2 tau qhia ntau heev thaum tib neeg kis WNV. CCL2 gene qhia yog upregulated nyob rau hauv lub hlwb cov ntaub so ntswg ntawm cov neeg mob uas succumb rau WNV encephalomyelitis [56]. Raws li, CCL2 ntau lawm tau nce siab hauv cov ntshav ntawm cov neeg mob WNV-kab mob [124], nrog rau cov txiv neej cov ntshav pub ntshav muaj ntau dua CCL2 ntau dua li cov poj niam cov ntshav pub ntshav nyob rau theem tom qab IgM [33]. Tsis tas li ntawd, qhov nce ntawm CCL2 nyob rau theem tom qab-IgM seroconversion tau cuam tshuam nrog kev txhim kho cov tsos mob tshwm sim tom qab tus kab mob WNV [33,34]. Thaum lub sij hawm WNV kab mob, Ccr2 activation induced mono cytosis nyob ntawm CCL2 thiab CCL7, tab sis tsis CCL12, thiab tiv thaiv nas los ntawm kev sib tw tuag feem ntau los ntawm kev tswj cov ntshav monocyte theem [44]. CCL2-kev hloov pauv monocyte hloov mus rau cov kab mob dermis thiab cov qog ntshav qab zib, nrog rau lawv rov qab los ntawm cov ntshav mus rau cov pob txha thiab lawv qhov sib txawv rau DCs thaum lub sijhawm ntxov hauv WNV-mob nas [89]. CCL2 kuj tau kho qhov sib txuam ntawm cov kab mob inflammatory monocytes hauv lub hlwb, thiab lawv qhov sib txawv rau microglia txo qis kev muaj sia nyob, yog li ua lub luag haujlwm pathogenic hauv WNV encephalitis [90]. Txawm li cas los xij, hauv lwm txoj kev tshawb fawb siv cov qauv murine, CCL2 tsuas yog ib feem ntawm kev nrhiav neeg ua haujlwm monocyte thiab tsis ua lub luag haujlwm tseem ceeb hauv kev ciaj sia tom qab kev sib tw tuag [45]. Hauv qhov sib piv, CCL7 tsis muaj peev xwm ua rau muaj kab mob ntau ntxiv hauv lub hlwb, txhim kho kev tuag, thiab ncua kev tsiv teb tsaws ntawm neutrophils thiab CD8+ T hlwb rau hauv CNS [45]. CCL7 tau txo qis hauv tib neeg nrog qhov tshwm sim tsis zoo dua li piv rau cov neeg uas tau txais txiaj ntsig zoo dua tom qab IgM theem [34]. Thaum lub luag haujlwm ntawm CCL2 hauv WNV pathogenesis tseem tsis tau daws, CCL7 zoo li muaj txiaj ntsig zoo, txhim kho qhov tshwm sim ntawm WNV kab mob.

3.1.2. CCL3, CCL4, thiab CCL5 (Ccr5 Agonists)

CCR5 thiab nws cov kev cuam tshuam nrog chemokine ligands mediate chemotactic kev ua haujlwm hauv leukocytes thiab koom nrog hematopoiesis thiab tiv thaiv kab mob [138]. CCL3, 4 thiab 5 chemokines khi rau chemokine receptor Ccr5 tsis tuaj yeem kuaj pom hauv tib neeg sera thaum ntxov thiab lig theem ntawm tus kab mob [34,124] tab sis tau mob siab rau hauv CNS ntawm cov nas tom qab kev sim WNV kab mob (Table S2). Hauv tib neeg, Ccr5 tsis muaj peev xwm tsis ua rau muaj tus kab mob WNV, tab sis ib zaug kis tau tus mob, cov neeg mob tuaj yeem ua rau muaj kev cuam tshuam tshwj xeeb los nthuav tawm qhov tshwm sim ntxov thiab lig yog tias lawv txoj haujlwm Ccr5 ploj lawm lossis thaiv [35,36,139]. Raws li cov kev tshawb pom no, cov kev tshawb fawb hauv nas piav qhia tias Ccr5 tsis muaj peev xwm ua rau muaj cov tsos mob tshwm sim thiab kev tuag tom qab subcutaneous kab mob nrog WNV, txawm hais tias Ccr5 tsis tas yuav tsum muaj kev tiv thaiv kab mob ntawm tes hauv thaj tsam [32,93]. WNV-mob Ccr5-/- nas muaj peev xwm txo qis heev los nrhiav cov tshuaj tiv thaiv kab mob mononuclear tshwj xeeb rau hauv lawv lub hlwb uas muaj WNV, nce BBB permeability, thiab nce qib ntawm Ccr5 ligands [32,93]. Tus kheej lub luag haujlwm ntawm Ccr5 ligands tseem tsis meej, vim tias tsis muaj cov qauv hauv vivo tau siv los hais txog lawv txoj kev koom tes rau WNV pathogenesis. Ib qho kev tshawb fawb hauv vitro tau piav qhia tias qhov induction ntawm CCL5 nyob rau hauv cov lus teb rau WNV kab mob tsis txaus los txhawb cov leukocyte transmigration nyob rau hauv lub endothelial txheej nyob rau hauv ib tug qauv ntawm BBB uas muaj ob lub endothelial hlwb thiab astrocytes [140].

3.1.3. CCL19 thiab CCL21 (Ccr7 Agonists)

Kev sib cuam tshuam ntawm Ccr7 thiab nws cov cognate ligands koom nrog hauv kev ua kom muaj kev mob thiab T-cell teb [141]. WNV kab mob hauv cov qauv murine txhawb nqa tias Ccr7 thiab ligands CCL19 thiab CCL21 tuaj yeem hloov kho ntawm qib gene [64,76,110] thiab pab txhawb rau tus tswv tsev tiv thaiv WNV. Chemokine receptor Ccr7 yog qhov tseem ceeb rau kev ciaj sia tom qab WNV kev sib tw tuag rau cov nas [46]. Tsis tas li ntawd, Ccr7 xav tau rau cov hlwb myeloid nkag mus rau hauv cov qog ntshav thiab txwv tsis pub lawv nkag mus rau hauv lub hlwb, pab tiv thaiv kab mob thiab txo cov kab mob ntawm cov cytokine ntau dhau [46].

3.2. CXC Chemokines

3.2.1. CXCL1-3, CXCL6-8 (Cxcr2 Agonists)

Cxcr2 ua lub luag haujlwm tsis txaus ntseeg hauv kev sib kho cov kev lag luam ntawm neutrophils, uas tau pom zoo tias yog tus neeg nqa khoom ntawm WNV hauv cov ntshav [49]. Cov nas uas tsis muaj Cxcr2 muaj qhov kev tuag zoo sib xws li cov nas qus, txawm hais tias lawv lub sijhawm tuag tau ncua [49]. Cxcr2 khi rau CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, thiab CXCL8 [114], uas yog tag nrho cov hloov kho los ntawm WNV kab mob (Table S2). CXCL8 yog upregulated nyob rau hauv WNV-infected thawj tib neeg kab lis kev cai [88] thiab cell kab [18,52,57,75,88,98] nrog rau cov hlwb thiab txha caj qaum kuaj los ntawm kev sim kab mob Rhesus liab (Macaca mulatta) [77]. Genes txuam nrog CXCL8 ntau lawm thiab upregulation tau induced nyob rau hauv New Zealand dawb luav (Oryctolagus cuniculus) [68]. CXCL8 tseem raug kuaj pom nyob rau theem siab hauv cov neeg muaj tus kab mob WNV [131,135]. Tsis tas li ntawd, cov neeg mob uas muaj cov tsos mob hnyav dua thaum lub sij hawm ntxov ntawm kev kis kab mob tau muaj ntau dua CXCL8 qhia hauv lawv cov ntshav thaum piv rau WNV-tsis zoo tswj [34]. Cov kev tshawb pom no qhia txog lub luag haujlwm tseem ceeb ntawm cov cytokine no hauv cov kab mob ntawm cov kab mob hauv tib neeg. Txawm li cas los xij, txog niaj hnub no, tsis muaj kev tshawb fawb hauv vivo tau tshawb xyuas qhov kev soj ntsuam no. Qhov no tuaj yeem piav qhia los ntawm qhov tsis muaj tseeb CXCL8 homologs hauv nas [142], uas tam sim no yog cov qauv tsiaj siv dav tshaj plaws los kawm WNV pathogenesis.

Siv lwm yam WNV qauv ntawm tus kab mob uas muaj ib tug ortholog CXCL8 noob, xws li luav [70,143–146] thiab nonhuman primates, [77,147] yuav tsim nyog los hla qhov teeb meem no.

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3.2.2. CXCL9 thiab CXCL10 (Cxcr3 Ligands)

Cxcr3 and its ligands are responsible for T-cell trafficking, activation, differentiation, and functions [48]. WNV natural infection in humans can induce high levels of CXCL9 [124] and CXCL10 [34,124,131,135] in the serum. Likewise, these chemokines were elevated following WNV infection in various experimental models (Table S2). Evidence from these models suggests that Cxcr3 signaling can have multifaced roles during WNV infection. In vitro, downregulation of neuronal CXCR3 signaling through TNF receptor 1 (TNFR1) decreased CXCL10 and resulted in apoptosis following WNV infection [99]. In vivo, Cxcr3 had no effect on WNV replication or clearance in peripheral lymphoid tissues [47]. However, CXCL10, but not CXCL9, and its cognate receptor Cxcr3 were required for survival after lethal WNV challenge and regulated the CD8+ T cells migration and clearing of WNV infection in the brain compared to control mice [47,48]. This can explain the evidence of both protective and deleterious effects of CXCL10 in humans. Higher susceptibility to WNV in blood donors was marked by lower levels of CXCL10/IP-10 during the post-IgM phase [33,34]. Importantly, analysis of autopsied neural tissues from humans with WNV encephalomyelitis revealed upregulation of the CXCL10-coding gene [56], and symptom development was positively correlated with CXCL10/IP-10 production during the earliest phase of the disease [34]. In later stages, significantly higher serum levels of CXCL10 were detected in patients with prolonged post-infection fatigue (>6 lub hlis) tom qab cov tsos mob ntawm tus kab mob WNV [132]. Yog li, CXCL10 kev hloov pauv los ntawm kev tsav tsheb tiv thaiv lub cev tiv thaiv cov lus teb rau cov neeg tsis zoo xav tau kev tshawb fawb ntxiv raws li lub hom phiaj kho tau.

3.2.3. CXCL12 (Cxcr4 Ligand)

Cxcr4 yog qhov nthuav dav tshaj plaws chemokine receptor thiab koom nrog hauv cell migration, hematopoiesis, thiab cell homing [148]. Kev hloov pauv hauv kev qhia ntawm Cxcr4 thiab nws cov canonical ligands CXCL12 tuaj yeem raug ntxias tom qab kev sim WNV kab mob (Table S2), thaum lawv cov qauv qhia hauv cov neeg mob WNV tseem tsis paub meej. Cov pov thawj tam sim no los ntawm kev sim kab mob qhia tias CXCL12 nyiam WNV neurospathogenesis. CXCL12 qhia, uas tau kho los ntawm IL-1 ntawm CNS microvasculature [54], txwv tsis pub nkag ntawm T cells ntawm BBB thiab tiv thaiv tus kab mob tshwj xeeb CD8+ T cells los ntawm kev tshem WNV hauv CNS parenchyma, ua rau muaj kev txhim kho kev tuag nyob rau hauv murine qauv ntawm tus kab mob [100].

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3.3. CX3C Chemokines

Chemokine CX3CL1 thiab nws cov receptor CX3CR1 tuaj yeem ua rau cov tshuaj tiv thaiv kab mob lossis tiv thaiv kab mob [149]. Lawv coding genes tau upregulated nyob rau hauv vivo tom qab WNV kab mob nyob rau hauv B6129PF2 thiab C57BL6/J nas [32] thiab Rhesus liab [77] (Table S2). Kev tshawb nrhiav hauv tus qauv murine tsis txhawb nqa lawv lub luag haujlwm uas pab kom muaj sia nyob tiv thaiv WNV kab mob [32].

4. Tumor Necrosis Factor Superfamily Ligands

Kev sib cuam tshuam ntawm TNFSF ligands thiab lawv cov cognate receptors tswj kev ciaj sia, kev loj hlob, kev sib txawv, thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob [111]. Ntawm TNFSF ligands, TNF- [72,99,103–105], Fas ligand (FasL) [39,76,110], TNF-related apoptosis-inducing ligand (TRAIL) [69,109,110], CD40L [85,111iv, acting (BAFF) [112], TNF ntsig txog qaug zog inducer ntawm apoptosis (TWEAK) [85], OX40L [117], thiab qog necrosis factor superfamily tus tswv cuab 14 (LIGHT) [76,150] yog cuam tshuam hauv WNV pathogenesis (Table S3).

4.1. Tumor Necrosis Factor

TNF-, ib qho cytokine muaj cov khoom tiv thaiv thiab tiv thaiv kab mob [151], muaj cov qauv qhia tsis sib xws tom qab WNV kab mob hauv tib neeg. Tib neeg sera tsom xam thaum WNV kub taub hau thiab WNV cov kab mob neuroinvasive tsis pom qhov hloov pauv hauv TNF- qhia [131], tab sis lwm tus piav qhia txog qhov tseem ceeb ntawm TNF-upregulation hauv WNV-cov neeg mob thaum lub sij hawm mob hnyav [124,130] thiab txawm tias ntev tom qab tus kab mob no tau kwv yees. tau tshem ntawm lub cev tiv thaiv kab mob [125]. TNF- tau ntau dua rau cov tib neeg uas muaj keeb kwm ntawm WNV kab mob thiab kev loj hlob ntawm cov kab mob raum ntev piv rau cov tib neeg noj qab haus huv [135]. Raws li cov ntaub ntawv tib neeg yav dhau los, yuav luag txhua qhov kev tshawb fawb siv cov qauv kev sim piav qhia txog kev nce TNF- thaum WNV kab mob (Table S3). Cov kev tshawb fawb soj ntsuam qhov tseem ceeb ntawm TNF- nyob rau hauv lub pathogenesis ntawm WNV kab mob qhia tau hais tias cytokine no muaj lub luag hauj lwm txwv nyob rau hauv kev tswj WNV kab mob nyob rau hauv peripheral organ [38,104], tsis muaj kev pom zoo hais txog lub teeb liab cascade thiab pab tswj WNV nyob rau hauv lub CNS (Table S3. ). Piv txwv li, TNF- receptor 1 (TNF-R1) signaling tau pom zoo downstream ntawm Tus Hu-zoo li receptor (TLR)-3, raws li TLR3 deficiency ua rau muaj kev cuam tshuam TNF- ntau lawm thaum WNV kab mob hauv microglia [67], tab sis tib qhov kev soj ntsuam tsis tshwm sim hauv cov pob txha pob txha-derived DCs [152]. Txawm li cas los xij, hauv ib txoj kev tshawb fawb, nas tsis muaj peev xwm ntawm TNF-R1 muaj kev tuag ntau dua li cov nas qus tom qab kev sib tw WNV [104], qhov tshwm sim tsis sib xws tau pom hauv lwm txoj kev tshawb fawb siv tib tus qauv [67]. Cov kev tshawb fawb yav dhau los tau qhia tias TNF- kev sib cuam tshuam nrog TNF-R1 tiv thaiv nas tiv thaiv WNV kab mob los ntawm kev tswj kev tsiv teb tsaws ntawm cov hlwb inflammatory mus rau hauv lub hlwb thaum kis mob [104], thaum tom kawg tau qhia tias TNF tuaj yeem ua lub luag haujlwm rau WNV neuroinvasion thaum ntxov. nce permeability ntawm BBB [67]. Kev txhaj tshuaj ntawm cov nas nrog cov kab mob qaub ncaug ua rau ntxov ntxov ntawm TNF- tom qab WNV kab mob, uas ua raws li kev ncua ntawm CNS tus kab mob thiab txo qis WNV hlwb titers piv rau cov nas mock-tiv thaiv kab mob [153], qhia txog lub luag haujlwm tiv thaiv thaum WNV encephalitis. Txawm li cas los xij, lwm txoj kev tshawb fawb tau piav qhia ntau dua TNF- qib uas tau lees paub qhov nce ntxiv ntawm cov kab mob neuroinvasive WNV sib txawv piv rau cov tsis-neuroinvasive variants hauv nas, [73] thiab TNF- tau koom nrog WNV-induced neurotoxicity [52]. Kev tshawb fawb ntxiv yog tsim nyog

4.2. TRAIL thiab FasL

TRAIL thiab FasL qhib apoptosis los ntawm cell nto tuag receptors [111]. Cov cytokines no tau tswj hwm ntawm cov qib noob siv hauv vivo qauv, suav nrog nas (Table S3). Hauv cov qauv nas, TRAIL pab txhawb rau kev daws teeb meem kab mob [38], thaum lub luag haujlwm ntawm FasL tseem tsis pom [28,39]. Hauv cov nas, TRAIL genetic deficiency ua rau muaj kev cuam tshuam rau WNV kev sib tw tuag, thiab CD8+ T cells ntsib teeb meem hauv kev tshem WNV los ntawm cov neurons [38]. WNV-induced qhia ntawm Fas hauv neurons, kev ua haujlwm FasL yuav tsum tau tiv thaiv IFN -deficient C57BL/6 nas los ntawm tus kab mob WNV, thiab CD8+ T hlwb siv FasL los txwv WNV kab mob hauv neurons [39]. Txawm li cas los xij, lwm txoj kev tshawb fawb siv tib cov nas uas tsis muaj nyob hauv Fas lossis FasL tsis pom qhov sib txawv ntawm kev tuag lossis kis kab mob hauv lub hlwb [28]. Cov txiaj ntsig tsis sib xws los ntawm cov kev tshawb fawb no tuaj yeem raug ntaus nqi rau qhov sib txawv ntawm cov kab mob sib kis (WNV 3000.0259 strain [39] piv rau WNV Sarafend strain [28]) nrog rau txoj hauv kev ntawm cov kab mob tsiaj (footpad [39] tiv thaiv kab mob [28]) .

4.3. CD40L

CD40L yog ib qho kev hloov pauv ntawm ntau yam kev lom zem thiab lub cev tiv thaiv kab mob [111] thiab tswj hwm los ntawm WNV kab mob hauv nas hlwb [64]. Hauv cov nas, CD40-CD40L kev sib cuam tshuam yuav tsum muaj rau kev tiv thaiv los ntawm kev sib tw WNV uas ua rau tuag taus, ua kom cov tshuaj tiv thaiv zoo los ntawm B hlwb, thiab T-cell tsiv teb tsaws thoob plaws BBB [40]. Thaum muaj pov thawj los qhia txog lub luag haujlwm rau CD40L hauv WNV kab mob, xav tau kev tshawb fawb ntxiv.

4.4. BAFF

BAFF yog xav tau rau peripheral B-cell ciaj sia taus thiab homeostasis thiab yog upregulated nyob rau hauv nas neutrophils thiab DCs tom qab WNV kev sib tw [112]. BAFF signaling yog qhov tseem ceeb rau kev muaj sia nyob tiv thaiv tus kab mob WNV tuag rau cov nas [41]. BAFF los ntawm DCs, tsis yog neutrophils, pab txhawb los yog txhawb nqa B-cell humoral cov lus teb rau WNV txij thaum WNV cov tshuaj tiv thaiv tshwj xeeb tau txo qis hauv cov nas uas tsis muaj BAFF qhia ntawm DCs [112]. Tsis tas li ntawd, BAFF receptor-tsis muaj nas tuaj yeem raug tus kab mob WNV tab sis tuaj yeem txhim kho kev tiv thaiv kev tiv thaiv thaum kho nrog kev tiv thaiv kab mob los ntawm cov nas qus uas muaj cov tshuaj tiv thaiv rau WNV [41].

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cistanche cog-nce kev tiv thaiv kab mob

5. Cov lus xaus

Cytokine tus cwj pwm sawv cev rau kev nce qib loj hauv peb txoj kev nkag siab ntawm tag nrho cov kev cai ntawm WNV-tsav cov lus teb tiv thaiv kab mob. Cytokine signaling ntawm IL-1 , IL-23, IL-17A, CCL7, CXCL10, TRAIL, CD40L, thiab BAFF tiv thaiv kab mob WNV mob rau cov nas; IL-10 thiab IL-22 pab hauv WNV pathogenicity; IL-6 thiab IL-12 tsis muaj qhov tshwm sim thaum kis kab mob; thiab CCL2, TNF-, thiab FasL lub luag haujlwm tseem tsis tau paub. Kev txiav txim siab lub luag haujlwm ntawm ib qho cytokine tuaj yeem nyuaj thiab ua rau cov lus tseem ceeb tshaj plaws los ntawm kev tshuaj xyuas no: Ua ntej, cov ntsiab lus lom neeg, xws li cov khoom siv ntawm tes, lub hom phiaj, theem ntawm kev tiv thaiv kab mob, thiab muaj lossis tsis muaj lwm yam. cytokines cuam tshuam lawv cov qauv qhia thiab kev ua haujlwm. Cov xwm txheej sim, sib txawv ntawm cov kev tshawb fawb, xws li kab mob los yog kab mob, cov txheej txheem tshawb xyuas, thiab lub sij hawm-cov ntsiab lus ntawm kev sau cov qauv, kuj tseem piav qhia tsis sib xws, qee zaum cov txiaj ntsig tsis zoo txog lub luag haujlwm ntawm cytokines thaum kis WNV. Qhov thib ob, qhov tshwm sim ntawm WNV kab mob nyob ntawm tsis yog tsuas yog ntawm kev tshem tawm cov kab mob xwb tab sis kuj nyob ntawm qhov kev mob tshwm sim uas tau tsav los ntawm cytokines. Cov kab mob WNV nyob rau hauv tib neeg thiab cov tsiaj sim muab pov thawj tias pro-inflammatory cytokines, xws li IL-1 , TNF- , IL-12p70, CXCL10, thiab IL-6, tuaj yeem nce siab tom qab WNV yog cleared. Qhov no qhia tau hais tias kev kho mob zoo tiv thaiv kab mob WNV neuroinvasive yuav tsum suav nrog cov tshuaj tiv thaiv kab mob los kho cov kab mob inflammatory exacerbated thaum lub sij hawm mob hnyav thiab tiv thaiv lub paj hlwb mus sij hawm ntev, vim cov cytokines no txuas rau neuronal raug mob hauv ntau cov kab mob neurodegenerative [154] . Cov kev tshawb fawb yav tom ntej yog qhov tseem ceeb rau kev nkag siab txog kev tswj hwm ntawm cov cytokines tuaj yeem txhim kho txoj kev mob. Qhov no tuaj yeem ua tiav los ntawm kev kawm cov tshuaj uas twb muaj lawm lossis cov khoom me me tawm tsam cov cytokines tau hais los saum no, nrog rau kev txhim kho cov kev kho tshiab uas cuam tshuam nrog cov cytokine txoj hauv kev. Thaum kawg, qhov kev tshuaj xyuas no qhia txog qhov yuav tsum tau muaj kev tshawb fawb ntxiv rau hauv cov cytokines, xav txog qhov tseem ceeb ntawm kev noj qab haus huv uas lawv tswj hwm, uas yuav pab txheeb xyuas cov hom phiaj kho immunomodulatory tiv thaiv kab mob WNV neuroinvasive. Piv txwv li, lwm cov qauv kab mob yuav tsum tau tsim rau txoj kev tshawb fawb ntawm CXCL8, cuam tshuam rau hnub no los ntawm qhov tsis muaj tseeb homologs hauv nas thiab nas. Kev ua haujlwm ntxiv uas tsom mus rau kev nthuav tawm lub luag haujlwm ntawm cov cytokines tseem ceeb uas tau piav qhia los ntawm kev tshawb fawb tib neeg, xws li IL-15, CCL8, CCL11, CCL13, thiab CCL20 tau lees paub kom nkag siab txog lawv txoj kev koom tes rau kev tiv thaiv kab mob ntawm WNV.

Cov ntaub ntawv

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