Fink Marc Y, Maloney Jenny, Keselman Aleksander, Li Erqiu, Menegas Samantha, Staniorski Christopher, Singer Steven M
Department of Biology, Georgetown University, Washington, DC 20057.
Department of Biology, Georgetown University, Washington, DC 20057
Immunohorizons. 2019 Aug 27;3(8):412-421. doi: 10.4049/immunohorizons.1900041.
Infection with the intestinal parasite is one of the most common causes of diarrheal disease in the world. Previous work has demonstrated that the cells and mechanisms of the adaptive immune system are critical for clearance of this parasite. However, the innate system has not been as well studied in the context of infection. We have previously demonstrated that infection leads to the accumulation of a population of CD11b, F4/80, ARG1, and NOS2 macrophages in the small intestinal lamina propria. In this report, we sought to identify the accumulation mechanism of duodenal macrophages during infection and to determine if these cells were essential to the induction of protective immunity. We show that F4/80, CD11b, CD11c, CX3CR1, MHC class II, Ly6C, ARG1, and NOS2 macrophages accumulate in the small intestine during infections in mice. Consistent with this resident macrophage phenotype, macrophage accumulation does not require CCR2, and the macrophages incorporate EdU, indicating in situ proliferation rather than the recruitment of monocytes. Depletion of macrophages using anti-CSF1R did not impact parasite clearance nor development of regulatory T cell or Th17 cellular responses, suggesting that these macrophages are dispensable for protective immunity.
肠道寄生虫感染是全球腹泻病最常见的病因之一。此前的研究表明，适应性免疫系统的细胞和机制对于清除这种寄生虫至关重要。然而，在寄生虫感染的背景下，固有免疫系统尚未得到充分研究。我们之前已经证明，寄生虫感染会导致小肠固有层中一群CD11b、F4/80、精氨酸酶1（ARG1）和一氧化氮合酶2（NOS2）巨噬细胞的积累。在本报告中，我们试图确定十二指肠巨噬细胞在寄生虫感染期间的积累机制，并确定这些细胞对于诱导保护性寄生虫免疫是否至关重要。我们发现，在小鼠感染期间，F4/80、CD11b、CD11c、CX3CR1、MHC II类分子、Ly6C、ARG1和NOS2巨噬细胞在小肠中积累。与这种驻留巨噬细胞表型一致，巨噬细胞的积累不需要CCR2，并且巨噬细胞掺入了5-乙炔基-2'-脱氧尿苷（EdU），表明是原位增殖而非单核细胞的募集。使用抗集落刺激因子1受体（anti-CSF1R）耗尽巨噬细胞并不影响寄生虫清除，也不影响调节性T细胞或辅助性T细胞17（Th17）细胞反应的发展，这表明这些巨噬细胞对于保护性寄生虫免疫是可有可无的。
