期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.02317
关键词
MDSC; non-tuberculous mycobacteria; T cells; dendritic cells; iNOS; Nos2; Arg1
类别
资金
- German Research Foundation (DFG) [Ge522/6-1, Go983/4-1, CRC1181]
- Interdisciplinary Center for Clinical Research (IZKF, University Hospital Erlangen) [A63]
- European Union/BMBF (Infect-EraNet)
- German Federal Ministry of Education and Research (BMBF) [ZooMAPII: 01KI1003A, 01KI1003C]
- Georg Christoph Lichtenberg scholarship from the Lower Saxony Ministry of Science and Culture
- Deutsche Forschungsgemeinschaft
- University of Veterinary Medicine Hannover, Foundation
Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with immunomodulatory function. To study the mechanism by which MDSC affect antimicrobial immunity, we infected mice with two M. avium strains of differential virulence, highly virulent Mycobacterium avium subsp. avium strain 25291 (MAA) and low virulent Mycobacterium avium subsp. hominissuis strain 104 (MAH). Intraperitoneal infection with MAA, but not MAH, caused severe disease and massive splenic infiltration of monocytic MDSC (M-MDSC; Gr-1(int)CD11b(hi)CD11c(int)) expressing inducible NO synthase (Nos2) and bearing high numbers of mycobacteria. Depletion experiments demonstrated that M-MDSC were essential for disease progression. NO production by M-MDSC influenced antigen-uptake and processing by dendritic cells and proliferation of CD4(+) T cells. M-MDSC were also induced in MAA-infected mice lacking Nos2. In these mice CD4(+) T cell expansion and control of infection were restored. However, T cell inhibition was only partially relieved and arginase (Arg) 1-expressing M-MDSC were accumulated. Likewise, inhibition of Arg1 also partially rescued T cell proliferation. Thus, mycobacterial virulence results in the induction of M-MDSC that block the T cell response in a Nos2- and Arg1-dependent manner.
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