Proliferation of resident macrophages is dispensable for protection during Giardia duodenalis infections

Authors: FINK, MARK - Georgetown University; Maloney, Jenny; KESELMAN, ALEKSANDER - Georgetown University; LI, ERQUIU - Georgetown University; MENEGAS, SAM - Georgetown University; JONES, CHRISTOPHER - Georgetown University; SINGER, STEVEN - Georgetown University

Submitted to: ImmunoHorizons
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/6/2019
Publication Date: 8/27/2019
Citation: Fink, M.Y., Maloney, J.G., Keselman, A., Li, E., Menegas, S., Jones, C., Singer, S.M. 2019. Proliferation of resident macrophages is dispensable for protection during Giardia duodenalis infections. ImmunoHorizons. 3(8):412-421. https://doi.org/10.4049/immunohorizons.1900041.
DOI: https://doi.org/10.4049/immunohorizons.1900041

Interpretive Summary: The protist parasite Giardia duodenalis is one of the most common causes of diarrheal disease in the world. The adaptive immune response has been shown to be important for infection control and parasite clearance. However, the role of the innate immune response during Giardia infection is not well characterized. We have previously found a novel population of macrophages with accumulating in the mouse intestine during Giardia infection. In this study, we further characterized these cells and determined if they have a role in protective immunity to Giardia in a mouse model. We found that macrophages with a regulatory/resident phenotype accumulate in the small intestine in infected 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 did not impact parasite clearance nor development of Treg or Th17 cellular responses, suggesting that these macrophages are dispensable for protective Giardia immunity. As macrophages have roles in both immune activation and regulation, the characterization of these cells may provide important insights into host-parasite interactions during infection. This information will be of interest to other scientists and physicians working to control infections with this widespread parasite.

Technical Abstract: Infection with the intestinal parasite Giardia duodenalis 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 Giardia infection. We have previously demonstrated that Giardia infection leads to the accumulation of a population of CD11b+, F4/80+, ARG1+, NOS2+ macrophages in the small intestinal lamina propria. In this report, we sought to identify the accumulation mechanism of duodenal macrophages during Giardia infection and to determine if these cells were essential to the induction of protective Giardia immunity. We show that F4/80+, CD11b+, CD11cint, CX3CR1+, MHCII+, 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 Treg or Th17 cellular responses, suggesting that these macrophages are dispensable for protective Giardia immunity.