Abstract
IL-10 produced by CD4+ T cells suppresses inflammation by inhibiting T cell functions and the upstream activities of antigen presenting cells (APCs). IL-10 was first identified in Th2 cells, but has since been described in IFNγ-producing Tbet+ Th1, FoxP3+ CD4+ regulatory T (Treg) and IL-17-producing CD4+ T (Th17) cells, as well as many innate and innate-like immune cell populations. IL-10 production by Th1 cells has emerged as an important mechanism to dampen inflammation in the face of intractable infection, including in African children with malaria. However, although these type I regulatory T (Tr1) cells protect tissue from inflammation, they may also promote disease by suppressing Th1 cell-mediated immunity, thereby allowing infection to persist. IL-10 produced by other immune cells during malaria can also influence disease outcome, but the full impact of this IL-10 production is still unclear. Together, the actions of this potent anti-inflammatory cytokine along with other immunoregulatory mechanisms that emerge following Plasmodium infection represent a potential hurdle for the development of immunity against malaria, whether naturally acquired or vaccine-induced. Recent advances in understanding how IL-10 production is initiated and regulated have revealed new opportunities for manipulating IL-10 for therapeutic advantage. In this review, we will summarize our current knowledge about IL-10 production during malaria and discuss its impact on disease outcome. We will highlight recent advances in our understanding about how IL-10 production by specific immune cell subsets is regulated and consider how this knowledge may be used in drug delivery and vaccination strategies to help eliminate malaria.
Highlights
Malaria remains a major public health problem in tropical and sub-tropical regions of the world despite substantial efforts to reduce associated morbidity and mortality
In mouse models of malaria, a critical role for IL-27 signaling in the regulation of pro-inflammatory Th1 cell responses and suppression of immune-mediated pathology has been reported [80,81,82,83]
A study with P. chaubadi AS infection showed that Treg cells produced IL-10 during infection, Tr1 cells were the important source of IL-10 for protection against severe immune-mediated pathology, and that the generation of these Tr1 cells was dependent on IL-27 signaling, it was independent of IL21 [84]
Summary
Malaria remains a major public health problem in tropical and sub-tropical regions of the world despite substantial efforts to reduce associated morbidity and mortality. In mouse models of malaria, a critical role for IL-27 signaling in the regulation of pro-inflammatory Th1 cell responses and suppression of immune-mediated pathology has been reported [80,81,82,83].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
