| First Author | Mizutani T | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 3 | Pages | 106081 |
| PubMed ID | 36843852 | Mgi Jnum | J:352752 |
| Mgi Id | MGI:7441578 | Doi | 10.1016/j.isci.2023.106081 |
| Citation | Mizutani T, et al. (2023) Neutrophil S100A9 supports M2 macrophage niche formation in granulomas. iScience 26(3):106081 |
| abstractText | Mycobacterium infection gives rise to granulomas predominantly composed of inflammatory M1-like macrophages, with bacteria-permissive M2 macrophages also detected in deep granulomas. Our histological analysis of Mycobacterium bovis bacillus Calmette-Guerin-elicited granulomas in guinea pigs revealed that S100A9-expressing neutrophils bordered a unique M2 niche within the inner circle of concentrically multilayered granulomas. We evaluated the effect of S100A9 on macrophage M2 polarization based on guinea pig studies. S100A9-deficient mouse neutrophils abrogated M2 polarization, which was critically dependent on COX-2 signaling in neutrophils. Mechanistic evidence suggested that nuclear S100A9 interacts with C/EBPbeta, which cooperatively activates the Cox-2 promoter and amplifies prostaglandin E2 production, followed by M2 polarization in proximal macrophages. Because the M2 populations in guinea pig granulomas were abolished via treatment with celecoxib, a selective COX-2 inhibitor, we propose the S100A9/Cox-2 axis as a major pathway driving M2 niche formation in granulomas. |
