@Article{,
AUTHOR = {Eva Villamón, Daniel Gozalbo, Patricia Roig, Celia Murciano, José Enrique O’Connor, Didier Fradelizi, M. Luisa Gil},
TITLE = {Myeloid differentiation factor 88 (MyD88) is required for murine resistance to Candida albicans and is critically involved in Candida-induced production of cytokines},
JOURNAL = {European Cytokine Network},
VOLUME = {15},
YEAR = {2004},
NUMBER = {3},
PAGES = {263--271},
URL = {http://www.techscience.com/ECN/v15n3/66383},
ISSN = {1952-4005},
ABSTRACT = {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.},
DOI = {}
}