STAT1-Dependent Recruitment of Ly6CCCR2 Inflammatory Monocytes and M2 Macrophages in a Helminth Infection.

Signal Transducer and Activator of Transcription (STAT) 1 signaling is critical for IFN-γ-mediated immune responses and resistance to protozoan and viral infections. However, its role in immunoregulation during helminth parasitic infections is not fully understood. Here, we used STAT1 mice to investigate the role of this transcription factor during a helminth infection caused by the cestode and show that STAT1 is a central molecule favoring susceptibility to this infection. STAT1 mice displayed lower parasite burdens at 8 weeks post-infection compared to STAT1 mice. STAT1 mediated the recruitment of inflammatory monocytes and the development of alternatively activated macrophages (M2) at the site of infection. The absence of STAT1 prevented the recruitment of CD11bLy6CLy6G monocytic cells and therefore their suppressive activity. This failure was associated with the defective expression of CCR2 on CD11bLy6CLy6G cells. Importantly, CD11bLy6CLy6G cells highly expressed PDL-1 and suppressed T-cell proliferation elicited by anti-CD3 stimulation. PDL-1 cells were mostly absent in STAT1 mice. Furthermore, only STAT1 mice developed M2 macrophages at 8 weeks post-infection, although macrophages from both -infected STAT1 and STAT1 mice responded to IL-4 in vitro, and both groups of mice were able to produce the Th2 cytokine IL-13. This suggests that CD11bCCR2Ly6CLy6G cells give rise to M2 macrophages in this infection. In summary, a lack of STAT1 resulted in impaired recruitment of CD11bCCR2Ly6CLy6G cells, failure to develop M2 macrophages, and increased resistance against infection.