PubMed ID
22039448
UMMS Affiliation
Department of Medicine, Division of Infectious Diseases and Immunology
Date
10-19-2011
Document Type
Article
Subjects
Animals; Cryptococcus neoformans; Mice; Mice, Knockout; Myeloid Differentiation Factor 88; Receptors, Interleukin-1; Receptors, Interleukin-18; Toll-Like Receptor 9
Disciplines
Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences
Abstract
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.
Comments
Citation: Wang JP, Lee CK, Akalin A, Finberg RW, Levitz SM (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. doi:10.1371/journal.pone.0026232. Link to article on publisher's site
Copyright: © 2011 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.