| First Author | Wang JP | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 10 | Pages | e26232 |
| PubMed ID | 22039448 | Mgi Jnum | J:178086 |
| Mgi Id | MGI:5297279 | Doi | 10.1371/journal.pone.0026232 |
| Citation | Wang JP, et al. (2011) Contributions of the MyD88-Dependent Receptors IL-18R, IL-1R, and TLR9 to Host Defenses following Pulmonary Challenge with Cryptococcus neoformans. PLoS One 6(10):e26232 |
| abstractText | Signaling via the adapter protein, MyD88, is important in the host defense against Cryptococcus neoformans infection. While certain Toll-like receptors (TLRs) can enhance the clearance of Cryptococcus, the contributions of MyD88-dependent, TLR-independent pathways have not been fully investigated. We examined the roles of IL-1R and IL-18R in vivo by challenging C57BL/6 mice with a lethal strain of Cryptococcus. We found that the absence of IL-18R, but not IL-1R, causes a shift in the survival curve following pulmonary delivery of a virulent strain of C. neoformans (H99). Specifically, IL-18R-deficient mice have significantly shorter median survival times compared to wild-type mice following infection. Cytokine analysis of lung homogenates revealed that deficiency of IL-IR, IL-18R, or MyD88 is associated with diminished lung levels of IL-1beta. In order to compare these findings with those related to TLR-deficiency, we studied the effects of TLR9-deficiency and found that deficiency of TLR9 also affects the survival curve of mice following challenge with C. neoformans. Yet the lungs from infected TLR9-deficient mice have robust levels of IL-1beta. In summary, we found that multiple signaling components can contribute the MyD88-dependent host responses to cryptococcal infection in vivo and each drives distinct pulmonary responses. |
