Human helminth infections are synonymous with impaired immune responsiveness indicating suppression of host immunity. Using a permissive murine model of filariasis, Litomosoides sigmodontis infection of inbred mice, we demonstrate rapid recruitment and increased in vivo proliferation of CD4+Foxp3+ Treg cells upon exposure to infective L3 larvae. Within 7 days post-infection this resulted in an increased percentage of CD4+ T cells at the infection site expressing Foxp3. Antibody-mediated depletion of CD25+ cells prior to infection to remove pre-existing 'natural' CD4+CD25+Foxp3+ Treg cells, while not affecting initial larval establishment, significantly reduced the number of adult parasites recovered 60 days post-infection. Anti-CD25 pre-treatment also impaired the fecundity of the surviving female parasites, which had reduced numbers of healthy eggs and micro-filaria within their uteri, translating to a reduced level of blood microfilaraemia. Enhanced parasite killing was associated with augmented in vitro production of antigen-specific IL-4, IL-5, IL-13 and IL-10. Thus, upon infection filarial larvae rapidly provoke a CD4+Foxp3+ Treg-cell response, biasing the initial CD4+ T-cell response towards a regulatory phenotype. These CD4+Foxp3+ Treg cells are predominantly recruited from the 'natural' regulatory pool and act to inhibit protective immunity over the full course of infection.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Parasitic helminth
- T cells