Toll-like receptor-2 is essential in murine defenses against Candida albicans infections.
In this work, we studied the role of toll-like receptor-2 (TLR2) in murine defenses against Candida albicans. TLR2-deficient mice experimentally infected intraperitoneally (i.p.) or intravenously (i.v.) in vivo had very significant impaired survival compared with that of control mice. In vitro production of TNF-alpha and macrophage inhibitory protein-2 (MIP-2) by macrophages from TLR2-/- mice in response to yeasts and hyphae of C. albicans were significantly lower (80% and 40%, respectively; P <0.05) than production by macrophages from wild-type mice. This impaired production of TNF-alpha and MIP-2 probably contributed to the 41% decreased recruitment of neutrophils to the peritoneal cavity of i.p. infected TLR2-/- mice. In contrast, in vitro phagocytosis of yeasts and production of reactive oxygen intermediates (ROI) were not affected in macrophages from TLR2-/- animals. Our data indicate that TLR2 plays a major role in the response of macrophages to C. albicans, triggering cytokine and chemokine expression, and it is essential for in vivo protection against infection.
Villamón
Eva
E
Departamento de Microbiología y Ecología, Facultad de Ciencias Biológicas, Universitat de València, Edificio de Investigación, C/Dr. Moliner 50, 46100 Burjasot, Valencia, Spain
Gozalbo
Daniel
D
Roig
Patricia
P
O'Connor
José Enrique
JE
Fradelizi
Didier
D
Gil
M Luisa
ML
D000818:Animals; D002176:Candida albicans / Q000276:immunology / Q000472:pathogenicity*; D002177:Candidiasis / Q000276:immunology*; D002452:Cell Count; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005434:Flow Cytometry; D025301:Hyphae / Q000276:immunology; D007113:Immunity, Innate; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha