| pubmed-article:15542452 | pubmed:abstractText | We have studied the role of myeloid differentiation factor 88 (MyD88), the universal Toll-like receptor (TLR) adaptor protein, in murine defenses against Candida albicans. MyD88-deficient mice, experimentally infected in vivo, had a very significant impaired survival, and a higher tissue fungal burden when compared with control mice. The recruitment of neutrophils to the site of infection was also significantly diminished in MyD88-\- mice. In vitro production of proinflammatory cytokines such as TNF-alpha, IFN-gamma and IL-12p70, by antigen-stimulated splenocytes from mice intravenously infected with the low-virulence C. albicans PCA2 strain, could not be detected in MyD88-\- mice. This default of production of Th1 cytokines in MyD88-deficient mice correlated with a greatly diminished frequency of IFN-gamma-producing CD4 + T lymphocytes. Also, the frequency of IFN-gamma-producing CD8 + T lymphocytes was lower in MyD88-\- mice than in control mice. Although C. albicans-specific antibody titers in PCA2-infected mice appeared more quickly in MyD88-\- mice than in control mice, the MyD88-\- group was not able to maintain the Candida-specific IgM nor IgG titers at the third week of infection. The complexity of antigens recognized by sera from MyD88-\- mice was quite similar to that from infected control mice. Taken together, these data show that MyD88-\- mice are extremely susceptible to C. albicans infections, suggesting that MyD88-dependent signaling pathways are essential for both the innate and adaptive immune responses to C. albicans. | lld:pubmed |
