| First Author | Kerepesi LA | Year | 2005 |
| Journal | Infect Immun | Volume | 73 |
| Issue | 12 | Pages | 8291-7 |
| PubMed ID | 16299326 | Mgi Jnum | J:104303 |
| Mgi Id | MGI:3611646 | Doi | 10.1128/IAI.73.12.8291-8297.2005 |
| Citation | Kerepesi LA, et al. (2005) Protective immunity to the larval stages of onchocerca volvulus is dependent on Toll-like receptor 4. Infect Immun 73(12):8291-7 |
| abstractText | Toll-like receptor 4 (TLR4) has been shown to be important for the induction of Th2-dependent immune responses in mice. Protective immunity against larval Onchocerca volvulus in mice depends on the development of a Th2 immune response mediated by both interleukin-4 (IL-4) and IL-5. In addition, O. volvulus contains the rickettsial endosymbiont Wolbachia, which has molecules with lipopolysaccharide-like activities that also signal through TLR4. We therefore hypothesized that protective immunity to O. volvulus would not develop in C3H/HeJ mice which have a mutation in the Tlr4 gene (TLR4 mutant), either because of a decreased Th2 response to the larvae or because of the absence of a response to Wolbachia. TLR4-mutant mice were immunized against O. volvulus with irradiated third-stage larvae, and it was observed that Th2 responses were elevated based on increased IL-5 production, total immunoglobulin E (IgE) levels, antigen-specific IgG1 response, and eosinophil recruitment. Protective immunity, however, did not develop in the TLR4-mutant mice. The Th1 response, as measured by gamma interferon production from spleen cells, was comparable in both wild-type and TLR4-mutant mice. Furthermore, antibody responses to Wolbachia were absent in both wild-type and TLR4-mutant mice. Therefore, the defect in the development of a protective immune response against O. volvulus in TLR4-mutant mice is not due to loss of Th2 immunity or the response to Wolbachia but is due to an unidentified TLR4-dependent larval killing mechanism. |
