STAT1-Dependent Recruitment of Ly6C(hi)CCR2(+) 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 Taenia crassiceps 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 CD11b(+)Ly6C(hi)Ly6G(−) monocytic cells and therefore their suppressive activity. This failure was associated with the defective expression of CCR2 on CD11b(+)Ly6C(hi)Ly6G(−) cells. Importantly, CD11b(+)Ly6C(hi)Ly6G(−) 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 T. crassiceps-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 CD11b(+)CCR2(+)Ly6C(hi)Ly6G(−) cells give rise to M2 macrophages in this infection. In summary, a lack of STAT1 resulted in impaired recruitment of CD11b(+)CCR2(+)Ly6C(hi)Ly6G(−) cells, failure to develop M2 macrophages, and increased resistance against T. crassiceps infection.