Absence of functional TLR4 impairs response of macrophages after Candida albicans infection.
Candida albicans is recognized by phagocytic cells through a set of recognition receptors patterns. Recently, we showed the importance of TLR2 in the regulation of neutrophil survival after C. albicans infection. In the present work, we analyzed the involvement of TLR4 in the recognition of C. albicans by neutrophils and macrophages. Our results show that the absence of functional TLR4 resulted in lower chemotaxis of neutrophils to the site of infection, lower levels of TNF-α, CXCL1 and nitric oxide, and dissemination and persistence of the pathogen in lymph nodes and spleen. In vitro, the phagocytic activity, nitric oxide production and myeloperoxidase activity, CXCL1, IL-1β production by neutrophils from TLR4-defective mice were not changed. In contrast, macrophages from TLR4-defective mice demonstrated lower phagocytosis and lower levels of CXCL1, IL-1β and TNF-α. Together, these data demonstrate that TLR4 signals are important for the recognition of C. albicans by macrophages and their absence allows persistence of the infection.
Gasparoto
Thaís Helena
TH
Department of Biological Sciences, Bauru Dental School - University of São Paulo, Bauru, SP, Brazil.
Tessarolli
Vanessa
V
Garlet
Thiago Pompermaier
TP
Torres
Sérgio Aparecido
SA
Garlet
Gustavo Pompermaier
GP
da Silva
João Santana
JS
Campanelli
Ana Paula
AP
D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D002465:Cell Movement; D054360:Chemokine CXCL1 / Q000378:metabolism; D002633:Chemotaxis; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D008198:Lymph Nodes / Q000382:microbiology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D009569:Nitric Oxide / Q000378:metabolism; D013154:Spleen / Q000382:microbiology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054360:Chemokine CXCL1; D053583:Interleukin-1beta; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide