Myeloid Cells in the Immune Response to Giardia

Abstract

Abstract Infection with the protozoan parasite, Giardia, produces symptoms associated with intestinal distress, but does not induce intestinal inflammation. Long-term sequellae of this infection include malnutrition, Irritable Bowel Syndrome and Chronic Fatigue Syndrome. Previous work indicates that T-cells are critical for clearance of this parasite; however, it is unclear which cells are responsible for the activation of T-cells. As such, our goal was to examine the contribution of myeloid cells to Giardia immunity as possible T-cell activators, effector cells and/or immune regulators. Small intestinal lamina propria cells were isolated from Giardia-infected wild-type or CCR2 deficient mice. Flow cytometry was used to determine cell phenotypes and to monitor cytokine response. EdU labeling was used to examine in situ proliferation of resident macrophages. Lastly, wild-type mice were treated with an anti-CSF1R monoclonal antibody to deplete macrophage populations. Flow cytometry demonstrated that CD11b+, F4/80+, CD11cint, MHCII+, Ly6Cint, CX3CR1int cells accumulate in the small intestine and express ARG1 and NOS2 during infection. Intracellular cytokine staining revealed an increase in IL-10 with a concurrent decrease in TNF-α. Macrophage accumulation was the same in wild-type and CCR2-deficient mice, and EdU labeling suggested in situ proliferation of resident macrophages rather than recruitment of inflammatory monocytes. Mice treated with anti-CSF1R eliminated the parasites as well as control mice. This study demonstrates that macrophages with a regulatory phenotype accumulate in the small intestine during Giardia infections and may explain why intestinal inflammation is not present during Giardia infections.