IL-10: A Multifunctional Cytokine in Viral Infections

Figure 1

IL-10 role in viral infections. During acute infections, proinflammatory signals are produced by DCs after recognition of pathogen patterns. In parallel, NK cells recognizing pathogen patterns and/or stimulated by proinflammatory signals further enhance inflammation. In this proinflammatory context, DC can promote antiviral T cell responses that clear the infection. Activation of DC, T cells, and NK cells also results in the production of the immunoregulatory cytokine IL-10 to balance inflammation. In this context, IL-10 expression controls immunopathology and leads to the resolution of the inflammation and T cell responses once the pathogen is cleared. During persistent infections, the virus exploits the production of IL-10 by DCs to exhaust antiviral T cells. High IL-10 levels produced by DCs suppress their antigen presenting capacity and lead to inefficient T cell activation. Chronic antigen presence further exhausts T cells and induces IL-10 production. T cells therefore become “tolerant” to viral antigens and infection persists. To establish chronicity and latent infections, the virus produces viral IL-10 homologs that favor anti-inflammatory responses. In human cytomegalovirus infection, cytomegalovirus-encoded IL-10 (cmvIL-10) and latency-associated cytomegalovirus-encoded IL-10 (LAcmvIL-10) are produced in myeloid cells and impair their function. cmvIL-10 induces hIL-10 production in DCs, macrophages, and monocytes, impairs DC differentiation, and promotes M2 polarization of macrophages. LAcmvIL-10 also promotes hIL-10 production in DCs and monocytes and impairs monocyte presenting capacity. IL-10 viral homologs induce human IL-10 (hIL-10) production in myeloid cells that contributes to impairment of their antigen presenting cell (APC) function. This in turn probably limits anti-CMV T cells responses and promotes IL-10⁺ T cell development. Impaired APC function permits chronic infections, while IL-10⁺ T cells allow latent infections to persist.