| First Author | Taylor MD | Year | 2009 |
| Journal | Eur J Immunol | Volume | 39 |
| Issue | 1 | Pages | 192-206 |
| PubMed ID | 19089814 | Mgi Jnum | J:143735 |
| Mgi Id | MGI:3828884 | Doi | 10.1002/eji.200838727 |
| Citation | Taylor MD, et al. (2009) Early recruitment of natural CD4(+)Foxp3(+) Treg cells by infective larvae determines the outcome of filarial infection. Eur J Immunol 39(1):192-206 |
| abstractText | 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 microfilaria 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. |
