Mast cells are important for protective immunity to intestinal helminth infections and as mediators of allergic disease. Their role in protozoan infections is less well described. We have therefore analyzed mast cell responses and parasite control in mice infected with the protozoan Giardia lamblia. We also measured immunoglobulin A (IgA) responses to the parasite, as IgA can have a protective role in this model. c-kit w/wv mice failed to make parasite-specific IgA, mount a mast cell response, or eliminate the infection. Anti-c-kittreated C57BL/6 mice had normal IgA responses, lacked mast cell responses, had reduced interleukin-6 (IL-6) mRNA in the small intestine, and failed to control the infection within 10 days. IL-9-deficient mice had a significant but reduced mast cell response and still controlled the infection within 2 weeks. Interestingly, IL-6-deficient mice had enhanced mast cell responses yet failed to rapidly control the infection. However, prevention of mast cell responses in IL-6-deficient mice by anti-c-kit treatment did not lead to parasite elimination. Both IL-6-and IL-9-deficient mice had normal IgA production. IL-6-deficient mice had significant serum levels of mast cell mediators, histamine and mast cell protease 1, following infection. Together, these results show that mast cells are important for the rapid control of Giardia infections in mice. Furthermore, they show that IL-6 is not necessary for these mast cell responses. Instead, they suggest that mast cell production of IL-6 appears to be important for control of this infection.

No abstract

Supplemental Digital Content is Available in the Text.

BackgroundTrends in urbanization contribute to the growing global demand for raw construction materials. The health effects of load carrying among occupational groups that mine and carry sand and stone used for construction of roads and buildings remains poorly understood.MethodsWe conducted an exploratory cross-sectional study among a convenience sample of sand miners working at an excavation site on the Seti River in Pokhara, Nepal. Load carrying weight, duration, and frequency were used to categorize miners as having “low” or “high” load-carrying exposures. Probable musculoskeletal disorders (MSDs) were identified using self-reported symptoms of moderate to severe musculoskeletal pain, as well as physical examinations.ResultsThe average loads carried by female and male sand miners weighed 66.3 kg and 87.3 kg, respectively. Among all participants (N=42), 45.2% reported moderate to severe musculoskeletal pain in at least one body region and 16 (38.1%) had probable MSDs identified using specified case criteria. The prevalence of MSDs was lower among miners carrying, on average, heavier loads compared to those carrying lighter loads (ORa=0.29; 95% CI: 0.05, 1.8), possibly indicative of the healthy worker survival effect. Miners carrying loads for longer durations and frequencies had higher odds of MSDs compared with those carrying for shorter durations and frequencies.ConclusionDespite the pervasiveness of load carrying as an income generating activity throughout the developing world, these populations remain largely excluded from global occupational health agendas. Larger epidemiologic studies are needed to justify action to protect the health and safety of these unrecognized and understudied groups.