CD4+T cells recruit, then engage macrophages in cognate interactions to clearMycobacterium tuberculosisfrom the lungs

Abstract

SummaryIFN-γ-producing CD4+T cells are required for protection against lethalMycobacterium tuberculosis(Mtb) infections. However, the ability of CD4+T cells to suppressMtbgrowth cannot be fully explained by IFN-γ or other known T cell products. In this study, we show that CD4+T cell-derived IFN-γ promoted the recruitment of monocyte-derived macrophages (MDMs) to the lungs ofMtb-infected mice. Although the recruited MDMs became quickly and preferentially infected withMtb, CD4+T cells rapidly disinfected the MDMs. Clearance ofMtbfrom MDMs was not explained by IFN-γ, but rather by MHCII-mediated cognate interactions with CD4+T cells. These interactions promoted MDM expression of glycolysis genes essential forMtbcontrol. Thus, by recruiting MDMs, CD4+T cells initiate a cycle of bacterial phagocytosis,Mtbantigen presentation and disinfection in an attempt to clear the bacteria from the lungs.