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Segmented Filamentous Bacteria Are Potent Stimuli of a Physiologically Normal State of the Murine Gut Mucosal Immune System

机译:分段的丝状细菌是小鼠肠粘膜免疫系统生理正常状态的有力刺激。

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Segmented filamentous bacteria (SFB) are autochthonous bacteria inhabiting the intestinal tracts of many species, including humans. We studied the effect of SFB on the mucosal immune system by monoassociating formerly germfree C3H/HeN mice with SFB. At various time points during 190 days of colonization, fragment cultures of small intestine and Peyer’s patches (PP) were analyzed for total immunoglobulin A (IgA) and SFB-specific IgA production. Also, phenotypic changes indicating germinal center reactions (GCRs) and the activation of CD4+ T cells in PP were determined by using fluorescence-activated cell sorter analyses. A second group of SFB-monoassociated mice was colonized with a gram-negative commensal,Morganella morganii, to determine if the mucosal immune system was again stimulated and to evaluate the effect of prior colonization with SFB on the ability of M. morganii to translocate to the spleen and mesenteric lymph nodes. We found that SFB stimulated GCRs in PP from day 6 after monoassociation, that GCRs only gradually waned over the entire length of colonization, that natural IgA production was increased to levels 24 to 63% of that of conventionally reared mice, and that SFB-specific IgA was produced but accounted for less than 1.4% of total IgA. Also, the proportion of CD4+, CD45RBlow T cells, indicative of activated cells, gradually increased in the PP to the level found in conventionally reared mice. Secondary colonization with M. morganii was able to stimulate GCRs anew, leading to a specific IgA antibody response. Previous stimulation of mucosal immunity by SFB did not prevent the translocation of M. morganii in the double-colonized mice. Our findings generally indicate that SFB are one of the single most potent microbial stimuli of the gut mucosal immune system.
机译:分段丝状细菌(SFB)是居住在包括人类在内的许多物种的肠道中的土生细菌。我们通过将以前无菌的C3H / HeN小鼠与SFB单关联研究了SFB对粘膜免疫系统的影响。在定居190天的各个时间点,分析了小肠和Peyer斑块(PP)的片段培养物的总免疫球蛋白A(IgA)和SFB特异性IgA的产生。此外,通过荧光激活细胞分选分析确定表明PP中的生发中心反应(GCR)和CD4 + T细胞活化的表型变化。用革兰氏阴性菌 Morganella morganii 定植第二组与SFB单亲相关的小鼠,以确定是否再次刺激了粘膜免疫系统,并评估了先前用SFB定植对这种能力的影响。的 M。 morganii 易位至脾和肠系膜淋巴结。我们发现SFB从单缔合后第6天开始刺激PP中的GCR,GCR仅在整个定殖过程中逐渐减弱,天然IgA产量增加到常规饲养小鼠的24%至63%,而且SFB特异性产生了IgA,但占总IgA的不到1.4%。同样,指示活化细胞的CD4 + ,CD45RB low T细胞的比例在PP中逐渐增加至常规饲养小鼠中发现的水平。用 M进行二次定殖。 morganii 能够重新刺激GCR,从而导致特异性的IgA抗体反应。 SFB先前对粘膜免疫的刺激并未阻止 M的移位。双重定植小鼠体内的摩根我们的发现通常表明,SFB是肠道粘膜免疫系统中最有效的微生物刺激之一。

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