Bacille Calmette-Guérin: Kev Pom Kev Pom Kev Pom Zoo Part 1
May 24, 2023
Abstract
Cov tshuaj tiv thaiv xws li cov kab mob bacilli Calmette-Guérin (BCG) paub txog lawv cov txiaj ntsig heterologous kho los ntawm ntau lub tswv yim, suav nrog kev cob qhia kev tiv thaiv uas tsim los ntawm monocyte-macrophage-based innate immunity. Lwm cov xwm txheej xws li kev sib kis ncaj qha hematogenous thiab induction ntawm autoimmunity kuj tau piav qhia.
Tau muaj kev txaus siab rov qab los siv qee qhov txiaj ntsig ntawm kev kawm tiv thaiv kab mob hauv kev tswj hwm COVID-19, txawm tias ntau cov tshuaj tiv thaiv tshwj xeeb tau pom zoo. Peb piav qhia lub sijhawm tam sim no kev paub txog cov teebmeem ntawm qhov muag ntawm BCG. Lub peev xwm cuam tshuam ntawm granulomatous o ntawm angiotensin-hloov enzyme kev ua thiab accentuation ntawm cytokine cua daj cua dub uas tej zaum yuav ua rau lub qhov muag tsis pom kev thiab cov teebmeem hauv lub cev kuj tau tham.
Bacillus Calmette-Guérin (BCG) yog ib qho tshuaj tiv thaiv uas txhawb lub cev tiv thaiv kab mob los ntawm kev txhaj tshuaj Bacillus Calmette-Guérin (BCG). BCG feem ntau yog siv los tiv thaiv tuberculosis, tab sis kuj tseem tuaj yeem tiv thaiv lwm yam kab mob thiab kab mob. Txawm li cas los xij, BCG tsis yog tib txoj hauv kev los txhawb kev tiv thaiv kab mob. Cov hauv qab no yog kev sib raug zoo ntawm cov tshuaj tiv thaiv BCG thiab kev tiv thaiv kab mob:
1. BCG tuaj yeem txhim kho kev tiv thaiv kab mob los ntawm kev ua kom lub cev tiv thaiv kab mob, ua rau lub cev muaj peev xwm tiv thaiv kab mob.
2. BCG tuaj yeem pab txhawb T-cell cov lus teb, uas yog qhov tseem ceeb rau kev sib ntaus sib tua, txhawb lub cev tiv thaiv kab mob.
3. BCG tseem tuaj yeem tawm tsam ntau yam kab mob los ntawm kev txhim kho lub peev xwm tua cov hlwb ib txwm muaj, ua rau tib neeg lub cev tsis muaj zog.
4. Txawm hais tias cov tshuaj tiv thaiv BCG muaj txiaj ntsig zoo hauv kev tiv thaiv kab mob, nws tsis yog panacea rau txhua yam kab mob. Yog li ntawd, kev txhim kho ntawm kev tiv thaiv yuav tsum yog los ntawm ntau txoj kev. Nrog rau kev txhaj tshuaj tsis tu ncua, tswj kev noj qab haus huv ntawm lub neej, xws li kev noj zaub mov kom zoo, pw tsaug zog zoo, qoj ib ce, thiab txo kev ntxhov siab tuaj yeem pab txhim kho lub cev tiv thaiv kab mob.
Hauv luv luv, BCG tuaj yeem txhim kho lub cev tiv thaiv kab mob los ntawm kev txhim kho kev ua haujlwm ntawm lub cev tiv thaiv kab mob, tab sis nws tsis yog tib txoj kev los txhim kho kev tiv thaiv kab mob. Peb yuav tsum tau txais ntau txoj hauv kev los txhawb kev tiv thaiv thiab tswj kev noj qab haus huv. Qhov no qhia txog qhov tseem ceeb ntawm kev txhim kho kev tiv thaiv kab mob. Cov polysaccharides hauv cov nqaij tuaj yeem tswj hwm lub cev tiv thaiv kab mob ntawm tib neeg lub cev, txhim kho kev ntxhov siab ntawm lub cev tiv thaiv kab mob, thiab txhim kho cov kab mob bactericidal ntawm lub cev tiv thaiv kab mob.
Nyem qhov txiaj ntsig kev noj qab haus huv ntawm cistanche
1. Taw qhia
Hauv ntau qhov chaw ntawm lub ntiaj teb no, tuberculosis (TB) ua rau muaj kev tuag tseem ceeb thiab mob, nrog rau kev cuam tshuam ntawm qhov muag. Hauv cov cheeb tsam uas muaj tus kab mob TB ntau, bacilli Calmette-Guérin (BCG) tuaj yeem txo qhov tshwm sim ntawm TB. BCG yog ib qho tshuaj tiv thaiv nyob rau hauv uas tau txais los ntawm Mycobacterium bovis uas tau tsim muaj ntau dua 13 xyoos los ntawm Fabkis tus kws kho kab mob Albert Calmette thiab Camille Guérin81.
Tom qab pib poob qis thaum sim ua kom muaj kev sib raug zoo ntawm bacilli ntawm glycerin thiab qos yaj ywm nruab nrab thiab kev cuam tshuam tom qab ntawm kev sim rau nyuj nrog kev sib kis ntawm Ntiaj Teb Tsov Rog Zaum Ib, lawv tau ua tiav hauv kev txo cov kab mob los ntawm kev ntxiv ox bile20. Cov tshuaj tiv thaiv qis qis tau pib hu ua bacilli bile Calmette-Guérin; Nyob rau hauv xyoo tsis ntev los, "bile" tau poob, thiab BCG tau pom zoo rau.
Kev tswj qhov ncauj tau raug xaiv rau tib neeg kev sim txij li Calmette suav hais tias txoj hnyuv plab yog txoj hauv kev ib txwm muaj kab mob los ntawm tubercle bacillus81. Calmette thiab Guérin tau raug kev thuam ntau hauv xyoo 1930 tom qab Lübeck kev puas tsuaj thaum lub sijhawm 72 tus menyuam mos tuag tawm ntawm 251 txhaj tshuaj tiv thaiv; Txawm li cas los xij, thaum lub sijhawm sim no xyoo 1931, kev tsis saib xyuas cov tshuaj tiv thaiv kab mob los ntawm cov kab mob virulent bacilli hauv Lübeck lub chaw soj nstuam tau ua pov thawj tias qhov ua rau, thiab cov tshuaj tiv thaiv tau raug tshem tawm 81. Qhov tshwm sim ntawm tuberculosis tom qab World Word II ua rau muaj ntau yam kev tshawb fawb ua pov thawj qhov muaj txiaj ntsig thiab ua tau zoo ntawm cov tshuaj tiv thaiv BCG.
Txawm hais tias nws siv dav, BCG tau cuam tshuam nrog cov teebmeem heterologous59,144. Lamm thiab cov neeg ua haujlwm tau tshuaj xyuas ntau dua 1000 cov ntawv tshaj tawm ntawm xyoo 1921 thiab 1982 uas tau tshaj tawm txog 10,000 qhov teeb meem ntawm kev txhaj tshuaj BCG65. Qhov xwm txheej ntawm qhov mob tshwm sim tsis tau paub tias feem ntau ntawm cov ntaub ntawv yog raws li cov ntaub ntawv xov xwm.
Ntau ntawm peb txoj kev nkag siab ntawm cov kev tsis zoo no ntawm BCG los ntawm nws txoj kev siv tshuaj intravesical (Intravesical BCG, IBCG) hauv kev kho mob qog noj ntshav, thaum lub sij hawm ntau lub voj voog ntawm BCG txhaj tshuaj. Tsis tas li ntawd, BCG yog siv los ua immunomodulator hauv kev kho mob melanoma. Cov ntawv thov hauv conjunctival malignancies kuj tau tshawb nrhiav.
Hauv qhov sib piv, qhov muaj txiaj ntsig zoo ntawm cov tshuaj tiv thaiv BCG txhawm rau txo tag nrho cov neeg tuag vim yog qhov tseem ceeb 6,45,51,54,116155. Kev txo qis hauv kev tuag los ntawm cov kab mob sib kis uas tsis yog tuberculosis xws li kab mob (Staphylococcus aureus), fungi (Candida albicans), thiab cov kab mob (cov kab mob khaub thuas daj) tau ua rau cov kws tshawb fawb tshawb fawb txog kev tiv thaiv kab mob ntawm cov teebmeem no62,63.
Kev txaus siab rov qab los ntawm kev siv cov txiaj ntsig zoo ntawm cov tshuaj tiv thaiv BCG kuj yog raws li cov qauv kev sib kis ntawm tus kabmob coronavirus (COVID-19) thiab txawv teb chaws txoj cai txhaj tshuaj tiv thaiv BCG156, txawm tias lub cev tsis muaj zog tuaj yeem ua rau immunopathology70.
Cov xwm txheej saum toj no nyob rau tam sim no tus mob hnyav ua pa nyuaj ua rau tus mob coronavirus2 (SARS-CoV-2) kis thoob qhov txhia chaw, ua rau peb tshuaj xyuas qhov tsis zoo ntawm BCG suav nrog ob qho tib si kis kab mob thiab tiv thaiv kab mob. Lub caij no, rau qhov tshuaj tiv thaiv tau pom zoo los ntawm WHO rau kev siv thaum muaj xwm ceev tiv thaiv COVID-19. Cov no yog tsim los ntawm Pfizer BioNTech, Moderna, Janssen, AstraZeneca / Oxford, Sinopharm, thiab Sinovac. Thawj peb ntawm cov no kuj tau pom zoo los ntawm USFDA158,157.
2. Kev tiv thaiv kab mob thiab mycobacteria
Innate tiv thaiv kab mob, tsim los ntawm monocyte-macrophage system, muab cov lus teb thawj zaug rau cov kab mob mycobacterial thiab ua rau muaj qhov dav dav "kev tiv thaiv kab mob" 6,63,67,98. Cov ntaub ntawv pov thawj rau kev tiv thaiv kev tiv thaiv saum toj no yog los ntawm cov kev tshawb fawb uas pom tias muaj ntau dua ntawm cytokines, xws li IL-1 , IL-6, IFN- , thiab TNF, teb rau ntau yam kab mob6,62– 64.
Heterologous tiv thaiv xav tau ob peb lub lis piam los txhim kho; Hloov chaw, ib qho epigenetic reprogramming ntawm lub cev tiv thaiv kab mob uas cuam tshuam nrog methylation ntawm histones tau raug npaj 62. Cov teebmeem no tseem muaj zog txawm tias tom qab ib xyoos tom qab txhaj tshuaj tiv thaiv. Ib yam tseem ceeb nyob rau hauv lub pathogenesis ntawm tubercular kab mob yog cov evasive tswv yim tsim los ntawm mycobacteria27,124.
2.1. Th1 thiab Th2 teb
Puas tau txij li Mossmann thiab cov neeg ua haujlwm tau piav qhia txog txoj hauv kev sib txawv ntawm CD4 ntxiv rau qhov tsis zoo Th0 cov hlwb rau hauv ob txoj kab hluav taws xob sib txawv, Th1 thiab Th2 hlwb, peb txoj kev nkag siab txog cov lus teb ntawm lub cev tiv thaiv kab mob rau cov kev sib tw immunologic sib txawv tau hloov zuj zus 58,93,128. . Los ntawm lub neej ntawd, phagocytose microbes suav nrog mycobacteria ua rau Th1 cov lus teb, pib los ntawm kev tso tawm ntawm IL-2.
Tom qab ntawd, mature Th1 hlwb secrete IFN- , thiab LT- (Fig 1). Raws li cov kab mob mycobacteria raug rhuav tshem, muaj qhov maj mam hloov mus rau Th2 teb los ntawm ntau lub cell divisions58. Sib nrug los ntawm stimulating phagocytosis, IFN- induces oxidative tawg, intracellular tua ntawm microbes, thiab qhia ntawm chav kawm I thiab chav kawm ntawv II loj histocompatibility complex (MHC) molecules ntawm ntau lub hlwb, xws li endothelial hlwb, keratinocytes, thiab fibroblasts. Lawv kuj txhawb nqa adhesion molecule qhia ntawm endothelial hlwb 38,58,78,98,133.
Hauv qhov sib piv, Th2 cov lus teb yog lub ntsiab lus teb rau cov uas tsis yog-phagocytose loj, cov kab mob extracellular xws li helminths (Fig 1). Th2 cells secrete IL-4, IL-5, IL-9, IL-10, thiab IL-13. Muaj ntau qhov sib tshooj hauv cov qauv ntawm cytokines secreted los ntawm Th1 thiab Th2 hlwb, tshwj xeeb tshaj yog IL-10 thiab IL13. Vim yog qhov sib tshooj no, ob qhov lus teb tau piav qhia los ntawm lawv lub peev xwm los zais IFN- lossis IL-4.
Qhov kawg ntawm Th2 teb yog B cell proliferation, antibody ntau lawm, thiab nws thiaj li hloov los ntawm IgG mus rau IgE antibodies. IgE titers qhia txog kev ntsuas tsis ncaj ntawm Th2 kev ua cuam tshuam hauv kev ua xua thiab atopic. Interestingly, Th1 thiab Th2 hlwb hla kev tswj ib leeg thiab tuaj yeem cuam tshuam los ntawm kev siv tshuaj kho mob lossis sib txawv thaum lub sijhawm hloov pauv ntawm cov kab mob sib kis75,78,131.Thaum mob ruas, paucibacillary tuberculoid leprosy yog ib qho kev tshwm sim ntawm kev ua phem Th1. , thaum tus mob lepromatous kawg ntawm tus mob ruas yog dominated los ntawm Th2 teb141,142.
Ib qho zoo sib xws dichotomy yog pom tseeb hauv kev tiv thaiv kab mob tiv thaiv Mycobacterium tuberculosis82,83. Yog li ntawd, cov neeg mob uas muaj tuberculosis nquag muaj cov lus teb tsis zoo ntawm cov xovtooj ntawm tes, ncua cov tshuaj tiv thaiv tsis zoo, thiab txo cov cell proliferation thiab IFN- ntau lawm hauv cov lus teb rau tuberculin lossis purified protein derivative (PPD); es cov neeg mob no tau pom ntau dua IL-482. Ib qho txiaj ntsig Th1 cov lus teb tau pom tseeb hauv Hom IV lossis qeeb qeeb, thaum Th2 cov lus teb pom hauv Tam sim ntawd lossis Hom I hypersensitivity.
2.2. Kev tiv thaiv kab mob rau BCG
Tshaj li ib puas xyoo, cov tshuaj tiv thaiv BCG tau muab rau ntau tshaj li peb txhiab tus menyuam yaus hauv Kev Tshawb Fawb Txog Kev Tiv Thaiv Kab Mob (EPI) thoob plaws txhua cheeb tsam152. Ntiaj teb no ib koob tshuaj tiv thaiv BCG yog muab rau kwv yees li 100 lab tus menyuam yug tshiab txhua xyoo 159. Ib txoj kev tshawb fawb Askiv tau tshaj tawm 50 feem pua kev tiv thaiv uas kav 20 xyoo 86. Txawm hais tias BCG tau pab txo qis kev tuag ntawm tus me nyuam mos tuberculosis, nrog rau kev tuag ntawm cov menyuam yaus, nws cov kev ua tau zoo ntawm cov neeg laus hauv kev tiv thaiv kab mob TB txawv ntawm 0-80 feem pua,3 thiab tsis muaj pov thawj zoo uas nws kav ntev dua 10 xyoo. tom qab txhaj tshuaj tiv thaiv.129Qhov kev zam yog haiv neeg Alaskan Indian zej zog uas nws kav ntev dua 50 xyoo. Hloov pauv, qhov tsis muaj kev tiv thaiv tag nrho kuj tau raug suav hais tias nyob hauv thaj chaw muaj xwm txheej hauv Is Nrias teb 7,90. Substrain variability, host genetics, noj zaub mov zoo, thiab muaj cov kab mob helminths sib koom tau raug suav tias yog kev piav qhia ntawm qhov sib txawv ntawm qhov ua tau zoo91,90,92,103,106.
Tsis tas li ntawd, kev tawm tsam ntawm T lymphocytes los ntawm TGF- thiab IL-10 tsim los ntawm kev tswj T hlwb (Tregs) hauv kev teb rau ib puag ncig mycobacteria tau raug pom zoo. Ib puag ncig mycobacteria tuaj yeem muaj qhov npog ntsej muag lossis thaiv cov nyhuv. Palmer thiab cov npoj yaig tau hais tias kev kis mus rau ntau qhov chaw ib puag ncig mycobacteria tuaj yeem muab qee qhov kev tiv thaiv kab mob thiab cuam tshuam rau lub cev tiv thaiv kab mob ntau yam, yog li npog cov nyhuv ntawm BCG106.
Hauv qhov sib piv, qhov thaiv qhov cuam tshuam txhais tau hais tias qhov kev tiv thaiv kab mob hauv cell-mediated rau ib puag ncig mycobacteria tshem tawm cov kab mob attenuated tom qab BCG inoculation109. Tsis tas li ntawd, cov menyuam yaus lub cev tsis muaj zog tiv thaiv kab mob hloov pauv ntawm qhov tsis zoo Th0 mus rau Th1 lossis Th2, tsis zoo li cov neeg laus uas tau tsim Th1/Th2 profile110.
Ntawm 21 substrains tsim los ntawm thawj hom kab mob, Denmark / Copenhagen strain 1331, Lavxias / Moscow, Nyiv / Tokyo 172 BCG, Pasteur 1173 P2, thiab Moreau RDJ hom kab mob rau ntau dua 90 feem pua ntawm cov tshuaj tiv thaiv BCG tau tswj hwm thoob ntiaj teb.30,159. Cov Pasteur 1173 P2 thiab Danish 1331 hom tshwm sim ua rau muaj kev cuam tshuam ntau dua 160.
2.3. Kev cuam tshuam ntawm kev tiv thaiv kab mob antimycobacterial
Qhov kev nkag siab saum toj no ntawm kev tiv thaiv kab mob antimycobacterial yog qhov tseem ceeb hauv kev kho mob. Ocular tuberculosis tsis muaj tus qauv ntsuas kub, thiab ntau qhov xwm txheej tseem muaj qhov xav tau. Kev sib txawv TB los ntawm lub zog sarcoid tseem nyuaj. Tsis tas li ntawd, tus qauv ntawm tubercular ocular o tuaj yeem sib txawv hauv cov neeg mob tiv thaiv kab mob lossis tiv thaiv kab mob. Vim tias nws qhov kev loj hlob qeeb, kab lis kev cai yuav siv sijhawm li kaum hnub, ua rau qeeb hauv lub tsev kho mob antitubercular. Thaum cov tshuaj tiv thaiv kab mob polymerase thiab interferon-gamma tso tawm (IGRA) muaj, cov kab ke kev noj qab haus huv hauv cov teb chaws tau nyiaj tsawg mus rau nruab nrab tseem cia siab rau PPD-raws li Mantoux xeem. Tsis zoo li IGRA, qhov kev xeem Mantoux tuaj yeem ua rau muaj kev cuam tshuam qeeb qeeb lossis hloov cov tshuaj tiv thaiv kab mob milieu18. Cov kev cuam tshuam tom qab ntawm qhov mob ntawm qhov muag tsis tau kawm dhau los, tshwj tsis yog cov ntaub ntawv sib cais 18,33.
Tsis tas li ntawd, kev txhaj tshuaj BCG ib yam nkaus tuaj yeem ua rau kev kuaj Mantoux zoo. Ntau qhov xwm txheej ntawm paradoxical zuj zus ntawm ocular o nrog cov tshuaj antitubercular tau tshaj tawm 21,66. Qhov muaj ntau ntxiv ntawm tubercular antigens los ntawm kev tua ceev ceev ntawm mycobacteria lossis txhim kho lub cev tiv thaiv kab mob ua rau muaj tshwm sim xws li kev tiv thaiv kab mob tiv thaiv kab mob (IRIS), tseem hu ua immune recovery uveitis (IRU), tom qab siv tshuaj tua kab mob 12,5066.
Hloov pauv, thawj qhov kev tiv thaiv kab mob ntawm lub qhov muag tsis pom kev qee zaum nce mus rau qhov chaw kis kab mob 85. Cov xwm txheej zoo sib xws tau pom nyob rau hauv cov qauv thim rov qab ntawm mob ruas thiab cov tshuaj tiv thaiv Jarisch-Herxheimer ntawm syphilis19,140,141. Yog li, lub luag haujlwm ntawm qhov hnyav Th1 lus teb tsis raug txiav tawm ntawm kev rov sib tw nrog PPD.
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