TY - EJOU AU - Villamón, Eva AU - Gozalbo, Daniel AU - Roig, Patricia AU - Murciano, Celia AU - O’Connor, José Enrique AU - Fradelizi, Didier AU - Gil, M. Luisa TI - Myeloid differentiation factor 88 (MyD88) is required for murine resistance to Candida albicans and is critically involved in Candida-induced production of cytokines T2 - European Cytokine Network PY - 2004 VL - 15 IS - 3 SN - 1952-4005 AB - We have studied the role of myeloid differentiation factor 88 (MyD88), the universal Toll-like receptor (TLR) adaptor protein, in murine defenses against 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, experimen-tally 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-α, IFN-γ 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-γ-producing CD4 + T lymphocytes. Also, the frequency of IFN-γ-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. MyD88-deficient mice, experimen-tally 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-α, IFN-γ 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-γ-producing CD4 + T lymphocytes. Also, the frequency of IFN-γ-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. KW - TLR KW - MyD88 KW - Candida albicans KW - murine candidiasis KW - TNF-α KW - IL-12p70 KW - IFN-γ KW - antibodies DO -