IL-10R blockade enhances effector and memory CD4+ T cell responses during persistent bacterial infection (MPF6P.733)

Abstract

Abstract Several bacterial pathogens have evolved to establish persistent infection in their hosts through suppression of host immune responses. IL-10 has emerged as a key immune-regulator during infection with various pathogens. Ehrlichia are tick transmitted bacteria that establish persistent infection in their natural reservoir hosts. In the present study, we analyzed the role of IL-10 in the development of immune responses and subsequent long-term protection against persistent ehrlichial infection in a murine model. We demonstrate that IL-10 secretion leads to reduced inflammatory responses and bacterial clearance and it also inhibits antigen-specific effector and memory CD4+ T cell responses during persistent bacterial infection. We also found that IL-10 secretion had no significant effect on the antigen-specific CD8+ T cell population. We observed that therapeutic blockade of IL-10R enhanced the magnitude and functional capacity of antigen-specific effector CD4+ T cells that translated into increased and more effective memory responses and secondary recall response after bacterial re-challenge. Our results provide new insights into the mechanisms of bacterial persistence and support the idea that alternative immune-based strategies may have applications in persistent bacterial infections.