Modulation of malaria-induced immunopathology by concurrent nematode infection (46.8)

Abstract

Abstract Gastrointestinal nematode infections, highly prevalent in malaria endemic areas, are known to modulate host immune responses to unrelated pathogens. However, the complex relationship between worms and malaria and the impact on malarial incidence vs. severity are unclear. Previously, we observed that C57BL/6 (B6) mice infected with the gastrointestinal nematode Heligosomoides polygyrus (Hp) for 2 wks before blood-stage Plasmodium chabaudi AS (Pc) infection developed significantly higher parasitemia compared to mice infected with Pc alone. Despite this, malaria-induced body weight loss, anemia and hepatosplenic damage were not exacerbated in co-infected mice. Indeed, there was less severe hypothermia and hypoglycemia and more robust reticulocytosis in co-infected mice. Co-infection with Hp suppressed type 1 immune responses induced by P. chabaudi infection with significantly reduced plasma levels of IFN-γ, TNF-α and nitric oxide, but increased IL-6 and IL-10 levels. Co-infected STAT-6−/− mice, which have disrupted Th2 responses, experienced only slightly more severe hypothermia, hypoglycemia, and anemia than co-infected WT B6 mice while in vivo administration of anti-IL-10R (1B1.2) mAb resulted in higher mortality in co-infected WT mice. Although concurrent nematode infection resulted in increased parasitemia due to impaired anti-malarial type 1 immunity, our data suggest that malaria-associated pathology is alleviated by a complex immunoregulatory network, possibly involving IL-10, and, to a lesser extent, Th2 cytokines.