CD103+lung dendritic cells (LDCs) induce stronger Th1/Th17 immunity to a bacterial lung infection than CD11bhi LDCs

被引:34
|
作者
Shekhar, Sudhanshu [1 ,2 ]
Peng, Ying [1 ,2 ]
Wang, Shuhe [1 ,2 ]
Yang, Xi [1 ,2 ]
机构
[1] Univ Manitoba, Dept Med Microbiol, Fac Med, Winnipeg, MB, Canada
[2] Univ Manitoba, Dept Immunol, Fac Med, 471 Apotex Ctr,750 McDermot Ave, Winnipeg, MB R3E 0T5, Canada
基金
加拿大健康研究院;
关键词
Chlamydia muridarum; lung dendritic cell; Th1/Th17; cells; KILLER T-CELLS; CHLAMYDIA-TRACHOMATIS; PNEUMONIAE INFECTION; PROTECTIVE IMMUNITY; INFLUENZA-VIRUS; ORAL TOLERANCE; IFN-GAMMA; IN-VIVO; RESPONSES; PD-1;
D O I
10.1038/cmi.2016.68
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Recent studies suggest differential roles for CD103+ and CD11b(hi) lung dendritic cells (LDCs) in host defense against viral and bacterial infections. In this study, we examined the contribution of these LDC subsets in protective immunity to chlamydial lung infection using a Chlamydia muridarum mouse infection model. We found that CD103+ LDCs showed higher expression of costimulatory molecules (CD40, CD80 and CD86) and increased production of cytokines (IL-12p70, IL-10, IL-23 and IL-6) compared with CD11b(hi) LDCs, but the expression of programmed death-ligand 1 (PD-L1) was similar between the two subsets. More importantly, we found, in adoptive transfer experiments, that the mice receiving CD103+ LDCs from Chlamydia-infected mice exhibited better protection than the recipients of CD11b(hi) LDCs, which was associated with more robust Th1/Th17 cytokine responses. In addition, in vitro experiments showed that CD103+ LDCs induced stronger IFN-gamma and IL-17 responses, when cocutured with chlamydial antigen-primed CD4+ T cells, than CD11b(hi) LDCs. Furthermore, the blockade of PD1 in the culture of CD4+ T cells with either CD103+ or CD11b(hi) LDCs enhanced production of IFN-gamma and IL-17. In conclusion, our data provide direct evidence that CD103+ LDCs are more potent in promoting Th1/Th17 immunity to chlamydial lung infection than CD11b(hi) LDCs.
引用
收藏
页码:377 / 387
页数:11
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