Giardia increases macrophage production of the anti-inflammatory cytokine interleukin-10 in response to lipopolysaccharide via macrophage galactose binding lectin.

Giardia duodenalis is an intestinal protozoan parasite common in low- and middle-income countries. Infection is often subclinical, even when it is associated with other pathologies like growth stunting in children. Recent longitudinal cohort studies have found Giardia more frequently in patients with milder symptoms and have even suggested that Giardia reduces rotavirus symptom severity. One potential mechanism for limiting disease severity due to other enteropathogens is the promotion of anti-inflammatory responses that limit pathology. Our lab previously showed that Giardia reduces production of interleukin (IL)-12 by dendritic cells stimulated with Toll-like receptor agonists. In this study, we show that Giardia increases the production of the anti-inflammatory cytokine IL-10 by mouse peritoneal macrophages in response to bacterial lipopolysaccharide. This potentiation is specific to IL-10, as no changes were seen in the production of the proinflammatory cytokine tumor necrosis factor ɑ. Moreover, peritoneal macrophages from mice lacking macrophage galactose-binding lectin, a pathogen recognition receptor that has been previously shown to bind N-acetylgalactosamine, failed to increase IL-10 production after stimulation with Giardia and lipopolysaccharide. Giardia's immunoregulation of the IL-10 response may help us understand the parasite's role in reducing diarrheal severity.