Differential induction of Th2- And Th1-associated responses by filarial antigens and endosymbioticWolbachiain a murine model of river blindness

Abstract

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 the absence of Wolbachia induced IL-5 production and eosinophil infiltration, but not IFN-γ. Conversely, Wolbachia induced IFN-γ production and no migration of eosinophils. There was no difference in neutrophil infiltration. Together, these findings demonstrate a distinct Th-associated phenotype induced by filaria and Wolbachia.

Adjuvant-free immunization with infective filarial larvae as lymphatic homing antigen carriers

“…We demonstrate that parasitic nematode can be chemically equipped with an antigen of choice, and together with the intrinsic adjuvant properties of filarial larvae, can be used as a complete vaccine carrier that naturally targets the lymphatic system. The adjuvant properties of filarial larvae, which depend on particulate antigen release 48 , CpG or the parallel discharge of intracellular Wolbachia bacteria from dying nematode cells 17 , require in-depth analysis.…”

“…Wolbachia are invertebrate-specific intracellular bacteria that live in obligate mutualistic symbiosis with most filarial parasites, controlling their fertility and development 15 . When released by the necrotic cells of dying filariae, these gram-negative bacteria induce IgG2 and cellular Th1 and Th17 immune response against its own but also filarial antigens 8,16,17 .…”

“…The labeling process transformed self-guided skin-to-lymph node infective larvae into vaccine carriers. The intrinsic adjuvancy of dying filariae facilitates the stimulation of OVA-specific immunity via the release of nonpathogenic intracellular Wolbachia bacteria 17,23 , methylated CpG sequences of discretely methylated nematode DNA 18 , or the slow-release of OVA from particulates of the protease-resistant cuticle 20,24 . Furthermore, cuticle collagens are resistant to proteolysis because of the high concentration of unique, nonreducible di-and tri-tyrosine bonds 24 .…”