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STAT1-Dependent Recruitment of Ly6ChiCCR2+ Inflammatory Monocytes and M2 Macrophages in a Helminth Infection

Authors :
Mireya Becerra-Díaz
Yadira Ledesma-Soto
Jonadab E. Olguín
Angel Sánchez-Barrera
Mónica G. Mendoza-Rodríguez
Sandy Reyes
Abhay R. Satoskar
Luis I. Terrazas
Source :
Pathogens, Vol 10, Iss 10, p 1287 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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+Ly6ChiLy6G− monocytic cells and therefore their suppressive activity. This failure was associated with the defective expression of CCR2 on CD11b+Ly6ChiLy6G− cells. Importantly, CD11b+Ly6ChiLy6G− 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+Ly6ChiLy6G− cells give rise to M2 macrophages in this infection. In summary, a lack of STAT1 resulted in impaired recruitment of CD11b+CCR2+Ly6ChiLy6G− cells, failure to develop M2 macrophages, and increased resistance against T. crassiceps infection.

Details

Language :
English
ISSN :
20760817
Volume :
10
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Pathogens
Publication Type :
Academic Journal
Accession number :
edsdoj.ff009a6092f54af8b17431bdbcfd8852
Document Type :
article
Full Text :
https://doi.org/10.3390/pathogens10101287