Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Eur J Immunol. 2012 Jan;42(1):165-75. doi: 10.1002/eji.201141833. Epub 2011 Dec 12.
The hygiene hypothesis has suggested an inhibitory effect of infections on allergic diseases, but the related mechanism remains unclear. We recently reported that DCs played a critical role in Mycobacterium bovis Bacille Calmette-Guérin (BCG)-mediated inhibition of allergy, which depended on IL-12 and IL-10-related mechanisms. Here, we tested the hypothesis that BCG infection could modulate the function of DC subsets, which might in turn inhibit allergic responses through different mechanisms. We sorted CD8α(+) and CD8α(-) DCs from BCG-infected mice and tested their ability to modulate Th2-cell responses to ovalbumin (OVA) using in vitro and in vivo approaches. We found that both DC subsets could inhibit the allergic Th2-cell response in both a DC:T-cell co-culture system and after adoptive transfer. These subsets exhibited different co-stimulatory marker expression and cytokine production patterns and were different in inducing Th1 and Treg cells. Specifically, we found that CD8α(+) DCs produced higher IL-12, inducing higher Th1 cell response, while CD8α(-) DCs expressed higher ICOS-L and produced higher IL-10, inducing CD4(+) CD25(+) FoxP3(+) Treg cells with IL-10 production and membrane-bound TGF-β expression. The finding suggests that one infection may inhibit allergy by both immune deviation and regulation mechanisms through modulation of DC subsets.
卫生假说表明感染对过敏性疾病有抑制作用，但相关机制尚不清楚。我们最近报道称，树突状细胞（DCs）在卡介苗（BCG）介导的过敏抑制中发挥关键作用，这取决于 IL-12 和 IL-10 相关机制。在这里，我们检验了这样一种假设，即 BCG 感染可以调节 DC 亚群的功能，而这可能通过不同的机制抑制过敏反应。我们从 BCG 感染的小鼠中分离出 CD8α(+)和 CD8α(-) DCs，并使用体外和体内方法测试它们调节对卵清蛋白（OVA）的 Th2 细胞反应的能力。我们发现，这两个 DC 亚群都可以在 DC:T 细胞共培养系统和过继转移后抑制过敏 Th2 细胞反应。这些亚群表现出不同的共刺激标记物表达和细胞因子产生模式，并在诱导 Th1 和 Treg 细胞方面有所不同。具体来说，我们发现 CD8α(+) DCs 产生更高水平的 IL-12，诱导更高的 Th1 细胞反应，而 CD8α(-) DCs 表达更高水平的 ICOSL 并产生更高水平的 IL-10，诱导具有 IL-10 产生和膜结合 TGF-β表达的 CD4(+)CD25(+)FoxP3(+)Treg 细胞。这一发现表明，一种感染可能通过调节 DC 亚群，通过免疫偏差和调节机制来抑制过敏。
