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 CD3TCRαβ and CD3TCRαβ macrophages. Both cell subpopulations express on their cell surface HLA family molecules, but only the CD3TCRαβ macrophage subpopulation co-express CD1 family molecules and transmembrane TNF (tmTNF). CD3TCRαβ macrophages secrete IL-1β, IL-6 IP-10, and MCP-1 by both tmTNF- and CD3-dependent pathways, while CD3TCRαβ macrophages specifically produce IFN-γ, TNF, and MIP-1β by a CD3-dependent pathway. In this study, we also used a mouse model of BCG-induced pleurisy and demonstrated that CD3 myeloid cells (TCRαβ and TCRαβ 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.