Pulmonary defense mechanisms against opportunistic fungal pathogens.
Though of critical importance, nonimmune host defense mechanisms against aspergillosis and mucormycosis are not completely understood. Prevention of these infections presumably requires control of either spore germination and/or hyphal growth by the host. The data suggest that the host provides an important barrier to infection by control of spore or conidia germination, the critical step involving conversion of the fungus to its tissue-invasive form. The mechanisms of host defense against A. fumigatus are not strictly dependent on inhibition of conidia germination. Rather, pulmonary defense against Aspergillus appears to depend to a greater degree on early killing of fungal conidia by alveolar macrophages. In contrast, prevention of mucormycosis appears to require inhibition of fungal spore germination by the bronchoalveolar macrophage, thereby preventing conversion of the fungus to its hyphal form, although resident bronchoalveolar macrophages are unable to kill R. oryzae spores. Thus, host pulmonary defenses to Rhizopus and Aspergillus vary, even in normal animals. The tissue-invasive hyphal forms of the fungi which cause aspergillosis and mucormycosis are too large to be ingested by phagocytic cells. Although macrophages and monocytes can damage hyphae, the bulk of this role appears to fall upon the neutrophil. However, antihyphal mechanisms of neutrophils may not necessarily be identical for all types of hyphae. Moreover, interactions of several potential oxidative and nonoxidative antihyphal mechanisms may define the host's ability to limit fungal infections. In individuals where concentrations of oxidative or nonoxidative substances are limiting or suboptimal, interactions of mechanisms may be required for antihyphal activity, and studies of these interactions are important to gain better knowledge of the defense mechanisms against opportunistic mycoses in the intact host. In summary, at least two distinct lines of defense against Aspergillus and Rhizopus are known in the normal host. Alveolar macrophages kill Aspergillus conidia and prevent germination of Rhizopus spores. The neutrophil damages the hyphal form of Aspergillus and Rhizopus. Thus, neutrophils and monocytes or macrophages act as distinct components of host defenses against aspergillosis and mucormycosis, and they may also operate by different mechanisms. Both invasion of tissue and environmental contact with aspergilli and the Mucorales induce the production of antibodies to these organisms. However, any definite role of antibodies or B cell-dependent immunity in effective host defense against initial invasion is still in doubt. It appears that the natural resistance of the host to Aspergillus depends primarily upon nonimmune factors. However, if these factors are breached, it remains possible that humoral immunity may play a role in host defense by limiting hyphal growth, perhaps in conjunction with phagocytic cells. The importance of cell-mediated immunity in resistance to aspergillosis and mucormycosis is not yet understood. It appears that the initial susceptibility to lethal infection is substantially T cell independent.(ABSTRACT TRUNCATED AT 400 WORDS)
Waldorf
A R
AR
University of California, Berkeley.
D000818:Animals; D001228:Aspergillosis / Q000276:immunology; D002177:Candidiasis / Q000276:immunology; D003453:Cryptococcosis / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology*; D008172:Lung Diseases, Fungal / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009091:Mucormycosis / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D009894:Opportunistic Infections / Q000276:immunology*; D012233:Rhizopus / Q000276:immunology