W E Bullock

Immunological aspects of fungal pathogenesis.

The incidence of infection with the pathogenic fungi continues to escalate, especially in the era of the acquired immune deficiency syndrome. To the clinician, this heterogeneous group of organisms poses both a diagnostic and a therapeutic challenge. Consequently, growing numbers of investigators are seeking to elucidate the pathogenetic mechanisms involved in disease caused by medically important fungi. In this review, many of the recent scientific advances that have been made in the immunological aspects of the pathogenesis of fungal infections are presented. The topics covered include 1) the receptors for fungi on the surface of professional phagocytes; 2) the mechanisms for killing and growth inhibition of fungi by phagocytes; 3) the means by which fungi evade host defenses; 4) the role of humoral immunity in fungal infection; 5) immunoregulation in fungal infections; and 6) the influence of cytokines on host defenses against pathogenic fungi.

Correlative studies of blastogenic responses and interleukin 1 production by mononuclear cells from patients with zoopathogenic fungal infections

The production of interleukin 1 (IL 1) by adherent peripheral blood mononuclear cells (PBMC) was quantitated in 16 individuals infected with Histoplasma capsulatum or Blastomyces dermatitidis and 16 age-matched controls. In parallel, we measured blastogenic responses to phytohemagglutinin (PHA) by PBMC from patients and controls. Of the 16 patients, six had pulmonary histoplasmosis, six had disseminated histoplasmosis, two had pulmonary blastomycosis, and two had disseminated blastomycosis. At the time of study, none of the patients were receiving immunosuppressive agents or had an underlying debilitating illness. Proliferative responses by PBMC from patients to PHA were significantly (P less than 0.05) less than the mean response by PBMC from an equal number of controls. In the 16 controls, the increase in secretion of IL 1 by lipopolysaccharide (LPS)-stimulated adherent cells over unstimulated cells ranged from 18 to 40 units of IL 1 activity per 10(5) adherent cells. The increment in IL 1 levels between LPS-stimulated adherent PBMC and unstimulated cells was diminished (less than 18 units of IL 1 activity per 10(5) adherent cells) in five of the 16 patients. Diminished IL 1 secretion in response to LPS was associated with impaired PHA responses in four of 10 patients.