Heterogeneity in lung macrophage control ofMycobacterium tuberculosisis determined by T cells

Abstract

FollowingMycobacterium tuberculosisinfection, alveolar macrophages are initially infected but ineffectively restrict bacterial replication. The distribution ofM. tuberculosisamong different cell types in the lung changes with the onset of T cell immunity when the dominant infected cellular niche shifts from alveolar to monocyte-derived macrophages (MDM). We hypothesize that changes in bacterial distribution among different cell types is driven by differences in T cell recognition of infected cells and their subsequent activation of antimicrobial effector mechanisms. We show that CD4 and CD8 T cells efficiently eliminateM. tuberculosisinfection in alveolar macrophages, but they have less impact on suppressing infection in MDM, which may be a bacterial niche. Importantly, CD4 T cell responses enhance MDM recruitment to the lung. Thus, the outcome of infection depends on the interaction between the T cell subset and the infected cell; both contribute to the resolution and persistence of the infection.