Novel Strategies to Enhance Vaccine Immunity against Coccidioidomycosis.

摘要

Coccidioidomycosis is a potentially life-threatening respiratory mycosis endemic to the Americas and caused by inhalation of spores produced by the molds Coccidioides immitis and C. posadasii. The dry, air-dispersed infectious spores (arthroconidia) are derived from saprobic-phase filaments that grow in semidesert soil of the southwestern United States and arid regions of Mexico and Central and South America [1]. Coccidioides is a dimorphic ascomycetous fungus with distinct saprobic and parasitic phases and is classified in the order Onygenales together with other genera of pathogenic molds that include Histoplasma, Blastomyces, and Paracoccidioides. The clinical spectrum of disease caused by these environmental pathogens ranges from a mild infection that resolves spontaneously to a disseminated mycosis. Inhaled spores of Coccidioides are small enough to colonize the lowermost reaches of the respiratory tree. Nonhuman primates experimentally challenged by aerosolization with fewer than ten infectious propagules developed a severe form of the disease and died within four to six weeks [2]. The parasitic cycle of Coccidioides is unique among these medically important, dimorphic molds. Spores in the lungs germinate to form multinucleate spherules (.60 mm diameter) that are too large to be engulfed by host phagocytes. The contents of mature spherules differentiate into a multitude of propagative endospores. Production of indigestible spherules that display high fecundity during the endosporulation stage confound phagocytic defenses and augment survival of the fungus in the lungs. Mammalian innate immune defenses are further compromised by the ability of endosporulating spherules to generate an alkaline microenvironment at infection sites due to their release of ammonia, which contributes to the pathogen s virulence [3].