Giardia duodenalis: dendritic cell defects in IL-6 deficient mice contribute to susceptibility to intestinal infection

Abstract

Interleukin (IL)-6 is important in numerous infections. IL-6 can promote T cell survival and differentiation toward Th17 cells, as well as B cell proliferation and differentiation to plasma cells. Giardia duodenalis is a protozoan parasite that replicates in the lumen of the small intestine in humans and many other mammals resulting in diarrhea, cramps and developmental delays in children. IL-6 is required for control of this infection, but it is unclear what its role is or which cells are required to produce this cytokine to generate efficient immunity. We have analyzed infections in a series of chimeric mice in which specific cell types lacked the ability to produce IL-6 in order to determine which sources of IL-6 played an important role in controlling this infection. Analysis of bone marrow chimeras indicate that radiation-sensitive, bone-marrow derived cells must produce IL-6. T cell chimeras show that T cell production of IL-6 is not required. Finally, by transferring dendritic cells from wild-type mice into IL-6 deficient recipients, we show that dendritic cell defects are responsible for the inability of IL-6 deficient mice to respond to Giardia challenge.