Unique Macrophages Different from M1/M2 Macrophages Inhibit T Cell Mitogenesis while Upregulating Th17 Polarization

Mycobacterial infection induces suppressor macrophages (M Phi s), causing disease exacerbation. There are two major M Phi subsets (M1 and M2 M Phi s) that are phenotypically and functionally different. Here, we examined which of the M Phi subsets the mycobacterial infection-induced suppressor M Phi s (MIS-M Phi s) belong to. MIS-M Phi s down-regulated T cell production of Th1 and Th2 cytokines but markedly increased production of interleukin (IL)-17A and IL-22 through up-regulation of Th17 cell expansion. In this phenomenon, a novel M Phi population, which is functionally distinguishable from M1 and M2 M Phi subsets and possesses unique phenotypes (IL-12(+), IL-1 beta(high), IL-6(+), tumor necrosis factor (TNF)-alpha(+), nitric oxide synthase (NOS) 2(+), CCR7(high), IL-10(high), arginase (Arg)-1(-), mannose receptor (MR)(low), Ym1(high), Fizz(low), and CD163high), played central roles through the action of IL-6 and transforming growth factor (TGF)-beta but not IL-21 and IL-23. This new type of M Phi population was induced in infected mice and actively supported the in vivo expansion of Th17 cells.