Bladder resident macrophage subsets differently shape the response to urinary tract infection
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ABSTRACT:
PROVIDER: PRJNA622523 | ENA |
REPOSITORIES: ENA
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Project description:Resident macrophages are highly abundant in the bladder, playing key roles in directing immunity to uropathogens. Yet, whether they are heterogeneous, where they come from, and precisely how they respond to infection remain largely unknown. We identified two macrophage subsets in mouse bladders with distinct localization, protein expression, and transcriptomes. Using a model of urinary tract infection, we validated our transcriptomics analyses finding that one macrophage subset phagocytosed more bacteria and polarized to a more anti-inflammatory profile, whereas the other subset died rapidly after infection. After resolution of infection, tissue-resident macrophage subsets were partially replaced by monocyte-derived cells with distinct transcriptional profiles. Elimination of these macrophages led to a type 1 biased immune response to challenge infection. Our study brings considerably more knowledge about the biology of bladder resident macrophages and their response to primary and recurrent infection, which may have broader implications for macrophage subsets in other mucosal tissues.
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Project description: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.
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Project description:We aimed to investigate the role of urinary bladder shape which may potentially change with advancing age, increased waist circumference, pelvic ischemia, and loosening of the urachus on bladder emptying and UFR. We retrospectively investigated the medical records of 76 men. The patients were divided into two groups according to bladder shapes in MRI scan (cone and spheric shapes). There was a significant difference between the two groups in terms of IPSS, Qmax, Qave, and waist circumference. A positive correlation has been demonstrated between mean peak urinary flow rate measured with UFM and mean flow rate calculated using the CP. There was a significant difference between mean urinary flow rates calculated with CP of cone and sphere bladder shapes. The change in the bladder shape might be a possible factor for LUTS in men and LUTS may be improved if modifiable factors including increased waist circumference and loosening of the urachus are corrected.
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