Myeloid cell arg1 inhibits control of arthritogenic Alphavirus infection by suppressing Antiviral T cells
Autor(es): Burrack Kristina S, Tan Jeslin J L, McCarthy Mary K, Her Zhisheng, Berger Jennifer N, Ng Lisa F P, Morrison Thomas E
Resumo: Arthritogenic alphaviruses, including Ross River virus (RRV) - chikungunya virus (CHIKV), are responsible for explosive epidemics involving millions of cases. These mosquito-transmitted viruses cause inflammation - injury in skeletal muscle - joint tissues that results in debilitating pain. We previously showed that arginase 1 (Arg1) was highly expressed in myeloid cells in the infected - inflamed musculoskeletal tissues of RRV- - CHIKV-infected mice, - 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, - that high Arg1 expression levels were associated with high viral loads - disease severity. Depletion of both CD4 - 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 - infected musculoskeletal tissues, but not lymphoid tissues, following RRV infection in mice, including suppression of interferon-? - CD69 expression. Collectively, these data enhance our underst-ing of the immune response following arthritogenic alphavirus infection - suggest that immunosuppressive myeloid cells may contribute to the duration or severity of these debilitating infections.
Imprenta: PLoS Pathogens, v. 11, n. 10, p. e1005191, 2015
Identificador do objeto digital: 10.1371/journal.ppat.1005191
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Immune response ; Chikungunya virus - Immune response ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever
Data de publicação: 2015
