Myeloid Cell Arg1 Inhibits Control of Arthritogenic Alphavirus Infection by Suppressing Antiviral T Cells

PLoS Pathogens

Kristina S. Burrack¹  Mary K. McCarthy¹  Jennifer N. Berger¹  Thomas E. Morrison¹  Lisa F. P. Ng²  Jeslin J. L. Tan²  Zhisheng Her² 

[1] Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America;Singapore Immunology Network, Agency for Science, Technology, and Research, Singapore

关键词: T cells;    Cytotoxic T cells;    Muscle tissue;    Bone marrow cells;    Spleen;    Chikungunya virus;    Chikungunya infection;    Viral load;   

DOI  :  10.1371/journal.ppat.1005191

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Arthritogenic alphaviruses, including Ross River virus (RRV) and chikungunya virus (CHIKV), are responsible for explosive epidemics involving millions of cases. These mosquito-transmitted viruses cause inflammation and injury in skeletal muscle and joint tissues that results in debilitating pain. We previously showed that arginase 1 (Arg1) was highly expressed in myeloid cells in the infected and inflamed musculoskeletal tissues of RRV- and CHIKV-infected mice, and specific deletion of Arg1 from myeloid cells resulted in enhanced viral control. Here, we show that Arg1, along with other genes associated with suppressive myeloid cells, is induced in PBMCs isolated from CHIKV-infected patients during the acute phase as well as the chronic phase, and that high Arg1 expression levels were associated with high viral loads and disease severity. Depletion of both CD4 and CD8 T cells from RRV-infected Arg1-deficient mice restored viral loads to levels detected in T cell-depleted wild-type mice. Moreover, Arg1-expressing myeloid cells inhibited virus-specific T cells in the inflamed and infected musculoskeletal tissues, but not lymphoid tissues, following RRV infection in mice, including suppression of interferon-γ and CD69 expression. Collectively, these data enhance our understanding of the immune response following arthritogenic alphavirus infection and suggest that immunosuppressive myeloid cells may contribute to the duration or severity of these debilitating infections.

【 授权许可】

CC BY