CD3+ Macrophages Deliver Proinflammatory Cytokines by a CD3-and Transmembrane TNF-Dependent Pathway and Are Increased at the BCG-Infection Site

Macrophages are essential cells of the innate immune response against microbial infections, and they have the ability to adapt under both pro- and anti-inflammatory conditions and develop different functions. A growing body of evidence regarding a novel macrophage subpopulation that expresses CD3 has recently emerged. Here, we explain that human circulating monocytes can be differentiated into CD3(+)TCR alpha beta(+) and CD3(+)TCR alpha beta(-) macrophages. Both cell subpopulations express on their cell surface HLA family molecules, but only the CD3(+)TCR alpha beta(+) macrophage subpopulation co-express CD1 family molecules and transmembrane TNF (tmTNF). CD3(+)TCR alpha beta(+) macrophages secrete IL-1 beta, IL-6 IP-10, and MCP-1 by both tmTNF- and CD3-dependent pathways, while CD3(+)TCR alpha beta(-) macrophages specifically produce IFN-gamma, TNF, and MIP-1 beta by a CD3-dependent pathway. In this study, we also used a mouse model of BCG-induced pleurisy and demonstrated that CD3(+) myeloid cells (TCR alpha beta(+) and TCR alpha beta(-) cells) are increased at the infection sites during the acute phase (2 weeks post-infection). Interestingly, cell increment was mediated by tmTNF, and the soluble form of TNF was dispensable. BCG-infection also induced the expression of TNF receptor 2 on CD3(+) myeloid cells, which increased after BCG-infection, suggesting that the tmTNF/TNFRs axis plays an important role in the presence or function of these cells in tuberculosis.