STAT1-Dependent Recruitment of Ly6C hi CCR2 + Inflammatory Monocytes and M2 Macrophages in a Helminth Infection.

Autor: Becerra-Díaz M; Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Autónoma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico.; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Ledesma-Soto Y; Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Autónoma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico., Olguín JE; Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Autónoma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico.; Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de Mexico (UNAM), Av. De Los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico., Sánchez-Barrera A; Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Autónoma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico., Mendoza-Rodríguez MG; Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Autónoma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico., Reyes S; Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Autónoma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico., Satoskar AR; Department of Pathology, The Ohio State University, Columbus, OH 43210, USA., Terrazas LI; Unidad de Biomedicina, Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Autónoma de Mexico (UNAM), Av. De Los Barrios, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico.; Laboratorio Nacional en Salud FES-Iztacala, Universidad Nacional Autónoma de Mexico (UNAM), Av. De Los Barrios 1, Los Reyes Iztacala, Tlalnepantla 54090, Edo. de Mexico, Mexico.
Jazyk: angličtina
Zdroj: Pathogens (Basel, Switzerland) [Pathogens] 2021 Oct 06; Vol. 10 (10). Date of Electronic Publication: 2021 Oct 06.
DOI: 10.3390/pathogens10101287
Abstrakt: 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.
Databáze: MEDLINE
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