Early enhanced control of Plasmodium yoelii infection in IL-10-deficient mice is independent of IFN-γ, IL-12, and the humoral response.

The outcome of a Plasmodium infection depends on the timely regulation of the robust pro-inflammatory response required to eliminate the parasite, but this response can cause tissue damage if not properly controlled. Interleukin-10 (IL-10) is an important regulatory cytokine that prevents immunopathology during many Plasmodium infections; however, this protection comes at the expense of less effective parasite control. This is illustrated by infection with blood-stage Plasmodium yoelii, in which mice exhibit a lower parasite load in the absence of IL-10. However, the immune components that limit parasite burden in the absence of IL-10 remain poorly understood. Abolishing IL-10 led to a predicted increase in TH1 polarization and a higher production of IL-12 and interferon-γ (IFN-γ). However, the enhanced production of these cytokines did not explain the improved parasite control seen in Il10-/- mice. Loss of IL-10 signaling reduced the accumulation of germinal center B cells and plasmablasts in the spleen, indicating a role for IL-10 in supporting the humoral response. However, although B cells are essential for survival, they do not play a critical role in early parasite control in IL-10-deficient mice. Moreover, Il10-/- mice lacking IFN-γ and B cells can limit early parasite expansion, suggesting that IL-10 suppresses host-protective pathways beyond the functions of B cells and IFN-γ in parasite control.