Differential induction of Th2- and Th1-associated responses byfilarial antigens and endosymbiotic Wolbachia in a murine modelof river blindness

摘要

Immune responses to filarial parasites like the river blindness inducing Onchocerca volvulus are obscured by combined reactions to the filarial nematodes themselves and their endosymbiont bacteria Wolbachia. Overall, infection with filarial nematodes induces a strong Th2 response characterized by IL-5 production and to a lesser degree a Th1 response and IFNγ production. Neutrophil and eosinophil infiltration into the corneal stroma are hallmark features of Onchocerca volvulus stimulation in a mouse model of river blindness. To determine the splenic and corneal response to filarial antigens in the absence of Wolbachia, C57BL/6 mice were immunized subcutaneously with either endosymbiotic Wolbachia alone, a soluble extract from the filaria Acanthocheilonema viteae that does not contain Wolbachia, or both, and injected into the corneal stroma. Neutrophil and eosinophil infiltration into the cornea was assessed by immunohistochemistry. In addition, Th1- and Th2-associated responses to filaria or Wolbachia were investigated by determining IL-5 and IFN-γ production by splenocytes. We found that A. viteae in theabsence of Wolbachia induced IL-5 production and eosinophilinfiltration, but not IFN-γ. Conversely, Wolbachia inducedIFN-γ production and no migration of eosinophils. There was no difference inneutrophil infiltration. Together, these findings demonstrate a distinctTh-associated phenotype induced by filaria and Wolbachia.