Regulation of Candida albicans morphogenesis by tumor necrosis factor-alpha and potential for treatment of oral candidiasis.
BACKGROUND
Endogenous tumor necrosis factor-alpha (TNF-alpha) has a beneficial effect as an activation mediator of host defense against infection by the fungus Candida albicans (C. albicans). However, it is unclear whether exogenous TNF-alpha has a beneficial or detrimental effect against Candida.


METHODS
The direct effect of TNF-alpha on CO2-induced morphological transformation of C. albicans blastoconidia was examined in vitro and the effect of TNF-alpha was determined in a mouse model of oral candidiasis.


RESULTS
TNF-alpha suppressed hyphal formation from C. albicans blastoconidia directly and dose-dependently, whereas it did not affect the fungal budding rate at concentrations ranging from 0.01 to 10 microg/ml. In vivo, the oral administration of TNF-alpha significantly reduced the C. albicans CFU in tongue tissues of treated mice. Histopathologically, there was a decrease in the number and size of C. albicans fungi in the tongue tissues.


CONCLUSIONS
Since orally administered TNF-alpha suppressed fungal burden in the tongue tissue without significant detrimental effects, TNF-alpha has potential as a therapeutic agent against Candida.
Ohta
Hitomi
H
Biomedical Institute, Research Center, Hayashibara Biochemical Laboratories, Inc., 675-1 Fujisaki, Okayama, Japan. fujisaki@hayashibara.co.jp
Tanimoto
Tadao
T
Taniai
Madoka
M
Taniguchi
Mutsuko
M
Ariyasu
Toshio
T
Arai
Shigeyuki
S
Ohta
Tsunetaka
T
Fukuda
Shigeharu
S
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D002180:Candidiasis, Oral / Q000188:drug therapy* / Q000382:microbiology; D002245:Carbon Dioxide / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D014059:Tongue / Q000187:drug effects / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use*
D000935:Antifungal Agents; D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide