A review of innate and adaptive immunity to coccidioidomycosis

Abstract

Coccidioidomycosis is a human fungal disease cause by inhalation of aerosol spores produced by Coccidioides posadasii or Coccidioides immitis. This disease is a common cause of community-acquired pneumonia in the endemic areas of the Southwestern United States. It also can present as a life-threatening disease as the fungal cells disseminate to skin, bone, and central nervous system. The outcome of coccidioidomycosis is largely determined by the nature of host immune response to the infection. Escalation of symptomatic infections and increased cost of long-term antifungal treatment warrant a concerted effort to better understand the innate and adaptive immune responses and the genetics associated with coccidioidomycosis susceptibility. This knowledge can be harnessed for development of a human vaccine against Coccidioides and advance clinic management of this disease. This review discusses recently reported studies on innate and adaptive immunity to Coccidioides infection, Mendelian susceptibility to disseminated disease and progress toward a human vaccine against this formidable disease.

Figure 1.

A. Missense z-scores from EXAC of genes identified in DCM. Z-scores for genes with deleterious variants in DCM patients and population frequency <1% (open circles, n = 68) or 0.1% (filled squares, n = 51) were obtained from ExAC. Scores were binned in 0.5 increments and plotted as number of genes in bin / total genes. Dotted vertical line is mean z-score of 1.3. B. Ratio of variant frequency in African / African American populations versus variant frequency across all populations. Data derived from ExAC, August, 2016 release. This Figure is reproduced in color in the online version of Medical Mycology.