Chronic
viral infections lead to CD8(+) T cell exhaustion, characterized by impaired
cytokine secretion. Presence of the immune-regulatory
cytokine IL-10 promotes chronicity of Lymphocytic Choriomeningitis Virus (LCMV) Clone 13
infection, while absence of IL-10/IL-10R signaling early during
infection results in viral clearance and higher percentages and numbers of
antiviral,
cytokine producing T cells.
IL-10 is produced by several cell types during LCMV
infection but it is currently unclear which cellular sources are responsible for induction of viral chronicity. Here, we demonstrate that although dendritic cells produce
IL-10 and overall
IL-10 mRNA levels decrease significantly in absence of CD11c(+) cells, absence of
IL-10 produced by CD11c(+) cells failed to improve the LCMV-specific T cell response and control of LCMV
infection. Similarly, NK cell specific
IL-10 deficiency had no positive impact on the LCMV-specific T cell response or viral control, even though high percentages of NK cells produced
IL-10 at early time points after
infection. Interestingly, we found markedly improved T cell responses and clearance of normally chronic LCMV Clone 13
infection when either myeloid cells or T cells lacked
IL-10 production and mice depleted of monocytes/macrophages or CD4(+) T cells exhibited reduced overall levels of
IL-10 mRNA. These data suggest that the decision whether LCMV
infection becomes chronic or can be cleared critically depends on early CD4(+) T cell and monocyte/macrophage produced
IL-10.