A Novel Population of TCRαβ-expressing CD11bhighCD14+F4/80+ Macrophages induced by a Pathogenic Murine Malaria enhances phagocytosis of parasites

Abstract

Abstract Macrophages, a component of the innate immune system, are equipped with a wide array of invariant receptors that facilitate the host defense against invading pathogens via phagocytosis and the release of inflammatory cytokines, and help maintain tissue homeostasis by initiating the repair and remodeling processes. In malaria, macrophages perform both immune protective (parasite clearance) and pathogenic (severe malaria anemia and cerebral malaria) functions. Utilizing the virulent asexual stage Plasmodium berghei ANKA (Pb-A) parasite, which causes experimental cerebral malaria (ECM) in mice, we have identified a novel population of TCRαβ-expressing macrophages that expands during Pb-A infection and preferentially migrates to and sequesters in the brain during ECM. This novel population of macrophages is CD3−CD4−CD8− and has a Vβ TCR repertoire that is distinctly different from conventional T cells. We also find that optimal expression of combinatorial TCRαβ on CD11bhigh cells requires coexpression of CD14 and F4/80. In depth immunological studies demonstrate that macrophage TCRαβ induces proliferation, alters IL-4 and MIP1β production, and enhances phagocytosis of infected erythrocytes. Expansion and activation of TCRαβ+CD11bhighCD14+F4/80+ macrophages during malaria infection point towards a convergence of the innate and adaptive immune responses where both arms of the immune system cooperate to modulate the host response to invading pathogens. Our results suggest that targeting macrophage effector functions through vaccines and drugs should be explored as an approach to reduced malaria mortality and morbidity.