Giardia duodenalis potentiates macrophage IL-10 production in response to LPS

Abstract Giardia duodenalis is one of the world's most common intestinal parasites, with an estimated 280 million cases globally each year. Infections can cause diarrhea and cramps, although they are often subclinical. Interestingly, Giardia can have a protective effect and reduce the incidence of fatal diarrhea in co-infections with other enteric pathogens. In this study, we investigate the anti-inflammatory response to Giardia via the macrophage galactose lectin-type 1 (MGL1) receptor. Our reasons for choosing this receptor are three-fold: it is expressed on macrophages and some dendritic cells and plays a role in immune response to other pathogens, it has been shown to induce anti-inflammatory effects in the DSS colitis model, and it demonstrably binds galactose-containing carbohydrates, like the N-Acetylgalactosamine (GalNAc) present in the cell wall of Giardia cysts. We show that peritoneal macrophages isolated from wildtype C57BL/6 mice produce markedly more of the anti-inflammatory cytokine IL-10 when stimulated with lipopolysaccharide (LPS) and Giardia extract compared to LPS alone. The potentiated IL-10 response to Giardia is lost in peritoneal macrophages isolated from MGL1 receptor knockout mice or in extracts centrifuged at 10,000 X g. Elucidating this anti-inflammatory pathway not only promises a better understanding of giardiasis, which disproportionately affect lower-middle income communities. also might present opportunities to mimic the parasite in the treatment of a wide array of inflammatory diseases. Supported by a grant from NIH (R15 AI109591).