TNF receptors in murine Candida albicans infection: evidence for an important role of TNF receptor p55 in antifungal defense.
TNF mediates multiple biologic activities through two distinct cell surface receptors, TNFR-p55 and TNFR-p75. TNF plays an important role in nonspecific resistance against the fungus Candida albicans. We used transgenic mice deficient for TNFR-p55 or TNFR-p75 to investigate the role of the TNFR in antifungal defense. Mice deficient for TNFR-p55 have highly impaired ability to clear infection with C. albicans and readily succumb to the infection. Also mice deficient for TNFR-p75 had a significant reduction in their ability to clear the fungus although lethality was not increased. These data demonstrate that TNFR-p55 in particular, but also TNFR-p75, plays a definite role in defense against infection with C. albicans. In NMRI mice, infection with C. albicans resulted in a significant systemic release of soluble (s)TNFR-p75. Cyclophosphamide-induced granulocytopenia led to a reduction of sTNFR-p75 release, whereas levels of bioactive TNF in response to fungal infection were increased. Release of sTNFR-p55 was not affected by induction of granulocytopenia. These observations suggest that granulocytes are a source of sTNFR-p75, possibly contributing to regulation of TNF activity during infection with C. albicans.
Steinshamn
S
S
Institute of Cancer Research and Molecular Biology, University Medical Center, Trondheim, Norway.
Bemelmans
M H
MH
van Tits
L J
LJ
Bergh
K
K
Buurman
W A
WA
Waage
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002176:Candida albicans / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D002177:Candidiasis / Q000235:genetics / Q000401:mortality / Q000517:prevention & control*; D007113:Immunity, Innate / Q000235:genetics; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012995:Solubility
D000911:Antibodies, Monoclonal; D018124:Receptors, Tumor Necrosis Factor