Myeloid differentiation factor 88 (MyD88) is required for murine resistance to Candida albicans and is critically involved in Candida -induced production of cytokines.
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.
Villamón
Eva
E
Departamento de Microbiología y Ecología, Universitat de València, C/Dr. Moliner 50, 46100 Burjasot, Valencia, Spain.
Gozalbo
Daniel
D
Roig
Patricia
P
Murciano
Celia
C
O'Connor
José Enrique
JE
Fradelizi
Didier
D
Gil
M Luisa
ML
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology*; D002176:Candida albicans / Q000276:immunology* / Q000502:physiology; D002177:Candidiasis / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D007668:Kidney / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88; D009504:Neutrophils / Q000276:immunology; D011971:Receptors, Immunologic / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic