Cytokines and anti-fungal immunity.
In summary, we have defined a unique host resistance circuit that has not previously been investigated. For the host control of an opportunistic fungal pathogen such as C. albicans, we have definitive evidence to indicate that LGL can respond to C. albicans by producing key cytokines, i.e. TNF, IFNg, and GMCSF, to activate neutrophil function against C. albicans. The cytokine-producing LGL differs from the spontaneous tumoricidal LGL by being DR+; otherwise other markers are identical, i.e., CD2(+)-CD16+CD4-CD8-CD15-. From the point of view of the neutrophils, they can respond to these cytokines readily within 2 hr of activation and may utilize any of the 3 antifungal pathways, i.e., oxidative radical production, enzyme degranulation, and lactoferrin release, to control Candida. It is of importance to note that TNF and GMCSF have also been shown to have chemotactic properties on neutrophils (27,28). Thus, the cytokines produced by LGL may have bifunctional roles for PMN, in not only activating them but in mobilizing them to the site of fungal invasion. In addition, we have defined that C. albicans as well as the bacterial polysaccharide, LPS, can activate PMN to produce TNF. Since TNF is a neutrophil activating factor, this implies that neutrophils may self-regulate function in an autocrine manner or utilize released TNF to recruit neighboring PMN. The possibility exists that other cytokines may also be produced by neutrophils when activated with C. albicans. Future studies should indicate the true role of neutrophils in host resistance to infection and may lead to a new identity for neutrophils as an active participant in the afferent phase of the immune response rather than an end effector cell population, waiting for outside signals to mobilize and activate them.
Djeu
J Y
JY
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612.
D002176:Candida albicans / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology
D016207:Cytokines