Gut-resident CX3CR1 hi macrophages induce tertiary lymphoid structures and IgA response in situ
| Autor: | Maryknoll Palisoc, Sulei Xu, Jelena Nedjic, Natalia Shulzhenko, Changsik Shin, Richard R. Rodrigues, Sravya Kurapati, Indira Purushothaman, Iannis Aifantis, Eugene Lin, Sathi Babu Chodisetti, Zia Ur Rahman, Azree Zaffran Ashraf, Matthias Mack, Pingnian He, Balázs Koscsó, Chetna Soni, Kavitha Gowda, Yuka Imamura Kawasawa, Milena Bogunovic, Haoyu Sun, Andrey Morgun |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
education.field_of_study Immunology Population Inflammation C-C chemokine receptor type 7 General Medicine Dendritic cell Biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Immune system medicine Macrophage Mesenteric lymph nodes CXCL13 medicine.symptom education 030215 immunology |
| Zdroj: | Science Immunology. 5 |
| ISSN: | 2470-9468 |
| Popis: | 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, Nos2+CX3CR1lo, Ccr7+CX3CR1int (lymph migratory), and Cxcl13+CX3CR1hi (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 Cxcl13+CX3CR1hi 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+CX3CR1int 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. |
| Databáze: | OpenAIRE |
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