Koscso, Balazs and Kurapati, Sravya and Rodrigues, Richard R. and Nedjic, Jelena and Gowda, Kavitha and Shin, Changsik and Soni, Chetna and Ashraf, Azree Zaffran and Purushothaman, Indira and Palisoc, Maryknoll and Xu, Sulei and Sun, Haoyu and Chodisetti, Sathi Babu and Lin, Eugene and Mack, Matthias and Kawasawa, Yuka Imamura and He, Pingnian and Rahman, Ziaur S. M. and Aifantis, Iannis and Shulzhenko, Natalia and Morgun, Andrey and Bogunovic, Milena (2020) Gut-resident CX3CR1(hi) macrophages induce tertiary lymphoid structures and IgA response in situ. SCIENCE IMMUNOLOGY, 5 (46): eaax0062. ISSN 2470-9468,
Full text not available from this repository. (Request a copy)Abstract
Intestinal mononuclear phagocytes (MPs) are composed of heterogeneous dendritic cell (DC) and macrophage subsets necessary for the initiation of immune response and control of inflammation. Although MPs in the normal intestine have been extensively studied, the heterogeneity and function of inflammatory MPs remain poorly defined. We performed phenotypical, transcriptional, and functional analyses of inflammatory MPs in infectious Salmonella colitis and identified CX3CR1(+) MPs as the most prevalent inflammatory cell type. CX3CR1(+) MPs were further divided into three distinct populations, namely, Nos(2+)CX3CR1(lo), Ccr(7+)CX3CR1(int) (lymph migratory), and Cxcl(13+)CX3CR1(hi) (mucosa resident), all of which were transcriptionally aligned with macrophages and derived from monocytes. In follow-up experiments in vivo, intestinal CX3CR1(+) macrophages were superior to conventional DC1 (cDC1) and cDC2 in inducing Salmonella-specific mucosal IgA. We next examined spatial organization of the immune response induced by CX3CR1(+) macrophage subsets and identified mucosa-resident Cxcl73(+) CX3CR1(hi) macrophages as the antigen-presenting cells responsible for recruitment and activation of CD4(+) T and B cells to the sites of Salmonella invasion, followed by tertiary lymphoid structure formation and the local pathogen-specific IgA response. Using mice we developed with a floxed Ccr7 allele, we showed that this local IgA response developed independently of migration of the Ccr7(+)CX3CR1(int) population to the mesenteric lymph nodes and contributed to the total mucosal IgA response to infection. The differential activity of intestinal macrophage subsets in promoting mucosal IgA responses should be considered in the development of vaccines to prevent Salmonella infection and in the design of anti-inflammatory therapies aimed at modulating macrophage function in inflammatory bowel disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HOMING T-CELLS; DENDRITIC CELLS; SALMONELLA-TYPHIMURIUM; LY6C(HI) MONOCYTES; PEYERS-PATCHES; LAMINA-PROPRIA; ORAL TOLERANCE; DIFFERENTIATION; TISSUE; EXPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Mar 2021 04:19 |
| Last Modified: | 29 Mar 2021 04:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44786 |
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