engleski

IL-33-dependent immunosuppressive Treg responses to liver damage during MCMV infection

Regulatory T cells (Treg) are critical for preventing autoimmunity mediated by self- reactive T cells, but also in modulating immune responses to infections and therefore controlling balance between activation and tolerance. Murine cytomegalovirus (MCMV) is a herpesvirus with pathogenic potential that can induce high levels of viral replication and modulate antiviral responses. Thus, early immune mechanisms are essential in controlling virus replication and protecting the host from virus-induced pathology. Studies on Treg cells reveal their role in suppressing early NK and T cell responses activated by MCMV infection. However, absence of Treg cells does not influence viral clearance. Here we show that Treg cells are indispensable for preventing liver pathology induced by MCMV infection. In addition, their suppressive capacity is dependent on tissue alarmin, IL-33, which promotes Treg recruitment and function in liver of MCMV infected mice. Moreover, mice lacking IL-33 receptor, showed higher death rate mediated by stronger liver pathology after infection with high viral dose. This is a consequence of decreased infiltration of Treg cells and lower expression of anti-inflammatory IL-10 and TGF-β, compared to control mice. In the light of recent discovery of IL-33's importance for accumulation and maintenance of Treg cells in acute colitis model, our results suggest protective and homeostatic role of IL- 33 signaling in inflammation induced by MCMV infection.

Interleukin-33; mouse; mouse cytomegalovirus; ST2 protein; mouse; T-lymphocytes; regulatory

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