Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder
Open Access
- 27 November 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (48), eabc5739
- https://doi.org/10.1126/sciadv.abc5739
Abstract
Resident macrophages are abundant in the bladder, playing key roles in immunity to uropathogens. Yet, whether they are heterogeneous, where they come from, and how they respond to infection remain largely unknown. We identified two macrophage subsets in mouse bladders, MacM in muscle and MacL in the lamina propria, each with distinct protein expression and transcriptomes. Using a urinary tract infection model, we validated our transcriptomic analyses, finding that MacM macrophages phagocytosed more bacteria and polarized to an anti-inflammatory profile, whereas MacL macrophages died rapidly during infection. During resolution, monocyte-derived cells contributed to tissue-resident macrophage pools and both subsets acquired transcriptional profiles distinct from naïve macrophages. Macrophage depletion resulted in the induction of a type 1–biased immune response to a second urinary tract infection, improving bacterial clearance. Our study uncovers the biology of resident macrophages and their responses to an exceedingly common infection in a largely overlooked organ, the bladder.Funding Information
- Horizon 2020 Framework Programme (665807)
- Agence Nationale de la Recherche (ANR-17-CE17-0014)
- Agence Nationale de la Recherche (ANR-19-CE15-0015)
- Agence Nationale de la Recherche (ANR-19-CE15-0015)
- Agence Nationale de la Recherche (ANR-10-LABX-69-01)
- Agence Nationale de la Recherche (ANR-10-LABX-73)
- Fondation Schlumberger pour l’Education et la Recherche (FRM FSER 2017)
- Emergence(s) program from Ville de Paris (2016 DAE 190)
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