PMID:15322035

Citation	Yauch, LE, Mansour, MK, Shoham, S, Rottman, JB and Levitz, SM (2004) Involvement of CD14, toll-like receptors 2 and 4, and MyD88 in the host response to the fungal pathogen Cryptococcus neoformans in vivo. Infect. Immun. 72:5373-82
Abstract	The major capsular polysaccharide of Cryptococcus neoformans, glucuronoxylomannan (GXM), is recognized by Toll-like receptor 2 (TLR2), TLR4, and CD14. In these studies, mice deficient in CD14, TLR2, TLR4, and the TLR-associated adaptor protein, MyD88, were utilized to investigate the contribution of TLRs and CD14 to in vivo host defenses against C. neoformans. MyD88(-/-) mice had significantly reduced survival compared with wild-type C57BL/6 mice after intranasal (i.n.) and intravenous (i.v.) infection with live C. neoformans. CD14(-/-) mice had reduced survival when infected i.v., while TLR2(-/-) mice died significantly earlier after i.n. infection. Mortality was similar comparing TLR4 mutant C3H/HeJ mice and control C3H/HeOuJ mice following i.v. or i.n. challenge with C. neoformans. The course of pulmonary cryptococcosis was studied in more detail in the CD14(-/-), TLR2(-/-), and MyD88(-/-) mice. MyD88(-/-) mice infected i.n. had higher numbers of CFU in the lungs as well as higher GXM levels in the sera and lungs 7 days after infection than wild-type mice did. Surprisingly, there were no major differences in the levels of tumor necrosis factor alpha, interleukin-4 (IL-4), IL-10, IL-12p70, or gamma interferon in the lungs of C. neoformans-infected knockout mice compared with wild-type mice. Histopathologic analysis of the lungs on day 7 postinfection revealed minimal inflammation in all mouse groups. These studies demonstrate a major role for MyD88 and relatively minor roles for CD14 and TLR2 in the response to cryptococcal infection, with the decreased survival of MyD88(-/-) mice correlating with increased numbers of lung CFU and serum and lung GXM levels.
Links	PubMed PMC517466 Online version:10.1128/IAI.72.9.5373-5382.2004
Keywords	Adaptor Proteins, Signal Transducing; Animals; Antigens, CD14/metabolism; Antigens, Differentiation/metabolism; Cryptococcosis/immunology; Cryptococcosis/microbiology; Cryptococcosis/mortality; Cryptococcus neoformans/pathogenicity; Lung Diseases, Fungal/immunology; Lung Diseases, Fungal/microbiology; Lung Diseases, Fungal/mortality; Membrane Glycoproteins/metabolism; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Myeloid Differentiation Factor 88; Receptors, Cell Surface/metabolism; Receptors, Immunologic/metabolism; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptors
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