CD8α+ and CD8α- DC subsets from BCG-infected mice inhibit allergic Th2-cell responses by enhancing Th1-cell and Treg-cell activity respectively.
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.
Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Xiaoling
X
Gao
Hong
H
Bai
Jianjun
J
Cheng
Yijun
Y
Fan
Shuhe
S
Wang
Lei
L
Jiao
Nan
N
Xiu
Xi
X
Yang
D019264:Adoptive Transfer; D000818:Animals; D016827:CD8 Antigens / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005434:Flow Cytometry; D061148:Hygiene Hypothesis; D006967:Hypersensitivity / Q000276:immunology* / Q000517:prevention & control; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016827:CD8 Antigens; D012333:RNA, Messenger; D016753:Interleukin-10; D018664:Interleukin-12