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.

常驻巨噬细胞在膀胱中含量丰富，在对尿路病原体的免疫中起关键作用。然而，它们是否是异质的，它们来自哪里，以及它们如何应对感染仍然很大程度上未知。我们在小鼠膀胱中鉴定了两个巨噬细胞亚群，肌肉中的 MacM 和固有层中的 MacL，每个都具有不同的蛋白质表达和转录组。使用尿路感染模型，我们验证了我们的转录组分析，发现 MacM 巨噬细胞吞噬了更多的细菌并极化为抗炎特性，而 MacL 巨噬细胞在感染期间迅速死亡。在解决过程中，单核细胞衍生的细胞有助于组织驻留巨噬细胞池，并且两个亚群都获得了与幼稚巨噬细胞不同的转录谱。巨噬细胞耗竭导致对第二次尿路感染的 1 型偏向免疫反应的诱导，从而提高了细菌清除率。我们的研究揭示了常驻巨噬细胞的生物学及其对在很大程度上被忽视的器官膀胱中极其常见的感染的反应。