Defective Priming of CD4+ T Cell Responses During Pre-patent Schistosome Infection
Abstract
Schistosomes are intravascular helminths that affect approximately 200 million people throughout the tropics and subtropics. An early Th1 response to schistosome worms is replaced at roughly 6 weeks post infection by a robust Th2 granulomatous response initiated by egg deposition. The host immune response against schistosome worms is critical in mediating the subsequent adaptive response that controls egg-induced immuno-pathology and may have a role in host resistance and susceptibility to co-infections. Here we sought to investigate whether alterations in the innate immune response induced by schistosomes create an immuno-modulatory milieu permissive for parasite establishment and development. Our data show that pre-patent infection induces the expression of cytokines representative of Th1, Th2, and T regulatory responses and that, in addition to IFN-, CD4+ T cells stimulated with worm antigen produce IL-4 and IL-10. We have demonstrated that pre-patent infection causes host T cell responses to polyclonal stimulation to become hyporesponsive. Although T regulatory cells play a role in immune regulation by producing the regulatory cytokine IL-10, they are not indicated as a significant source and do not function to control Th1 responses during pre-patent schistosome infection. We provide evidence that schistosome infection leads to a reduction in host T cell responses to non-parasite antigen and that this loss of responsiveness is due to an inability of innate APCs to stimulate T cell proliferation and cytokine production. Our analysis of the innate APC response implicates CD11b+ mononuclear cells as the population of cells affected by this loss of T cell stimulatory capacity, where schistosome infection interferes with the ability of CD11b+ cells to act as antigen presenting cells and stimulate T cell responses.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 26, 2011
- Accession Number
- AD1013328
Entities
People
- Christine E. Ferragine
Organizations
- Uniformed Services University of the Health Sciences