TNF receptors in murine Candida albicans infection: evidence for an important role of TNF receptor p55 in antifungal defense
Steinshamn, S.; Bemelmans, M.H.; van Tits, L.J.; Bergh, K.; Buurman, W.A.; Waage, A.
Journal of Immunology 157(5): 2155-2159
1996
ISSN/ISBN: 0022-1767 PMID: 8757341 Document Number: 464603
Tumour necrosis factor (TNF) mediates multiple biological activities through 2 distinct cell surface receptors, TNFR-p55 and TNFR-p75. Transgenic mice deficient for TNFR-p55 or TNFR-p75 were used to investigate the role of the TNFR in antifungal defence. Mice deficient for TNFR-p55 had highly impaired ability to clear infection with C. albicans and readily succumbed to infection; mice deficient for TNFR-p75 had a significant reduction in their ability to clear the fungus although lethality was not increased. These results indicated that TNFR-p55 in particular, but also TNFR-p75, has a definite role in defence 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. It is suggested that granulocytes are a source of sTNFR-p75 and could contribute to regulation of TNF activity during infection with C. albicans.