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B Plays a Crucial Role for Organ Clearance of Candida albicans1
*
Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Kwangju, Korea;
Department of Immunology and Institute for Medical Sciences, Chonbuk National University Medical School, Chonju, Republic of Korea; and
Korean Research Institute of Chemical Technology, Daejon, Korea
In this study, we have investigated the mechanisms underlying organ
susceptibility to candida infection. Infection of BALB/c mice with
Candida albicans led to both an early (1–8 h) and late
(24–48 h) activation of NF-
B in the organs resistant to C.
albicans, including the lung and spleen. In susceptible organs
such as the kidneys, early activation of NF-B was not observed. The
kinetics of TNF-
mRNA expression paralleled those of NF-B
activation in all organs examined. Blocking the effects of endogenous
platelet-activating factor (PAF) by pretreatment with the PAF
antagonist BN50739 or antioxidants significantly reduced the early
activity of NF-B and TNF- mRNA expression, and increased the
recovery of C. albicans in the lung and spleen.
Importantly, administration of PAF 5 min prior to the infection
resulted in the appearance of early activities of NF-B and TNF-
mRNA expression, followed by a nearly complete clearance of the
organisms in the kidneys. Pretreatment with anti-TNF- Ab
resulted in an enhanced susceptibility to C. albicans, and
the PAF-mediated resistance was abrogated by anti-TNF- in all
organs examined. These data indicated that endogenously produced PAF in
response to C. albicans is a key molecule involved in the
early activation of NF-B, which, in turn, renders the organ
resistant to the fungus by promoting the production of
anti-candidal proinflammatory cytokines such as TNF-.
Susceptible organs, including the kidneys, lack the capacity to
generate a sufficient PAF-induced early NF-B response.
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