| First Author | Martin AT | Year | 2024 |
| Journal | PLoS Pathog | Volume | 20 |
| Issue | 2 | Pages | e1011502 |
| PubMed ID | 38377133 | Mgi Jnum | J:352331 |
| Mgi Id | MGI:7609395 | Doi | 10.1371/journal.ppat.1011502 |
| Citation | Martin AT, et al. (2024) Parasite-induced IFN-gamma regulates host defense via CD115 and mTOR-dependent mechanism of tissue-resident macrophage death. PLoS Pathog 20(2):e1011502 |
| abstractText | Host resistance to a common protozoan parasite Toxoplasma gondii relies on a coordinated immune response involving multiple cell types, including macrophages. Embryonically seeded tissue-resident macrophages (TRMs) play a critical role in maintaining tissue homeostasis, but their role in parasite clearance is poorly understood. In this study, we uncovered a crucial aspect of host defense against T. gondii mediated by TRMs. Through the use of neutralizing antibodies and conditional IFN-gamma receptor-deficient mice, we demonstrated that IFN-gamma directly mediated the elimination of TRMs. Mechanistically, IFN-gamma stimulation in vivo rendered macrophages unresponsive to macrophage colony-stimulating factor (M-CSF) and inactivated mTOR signaling by causing the shedding of CD115 (CSFR1), the receptor for M-CSF. Further experiments revealed the essential role of macrophage IFN-gamma responsiveness in host resistance to T. gondii. The elimination of peritoneal TRMs emerged as an additional host defense mechanism aimed at limiting the parasite's reservoir. The identified mechanism, involving IFN-gamma-induced suppression of CD115-dependent mTOR signaling in macrophages, provides insights into the adaptation of macrophage subsets during infection and highlights a crucial aspect of host defense against intracellular pathogens. |
