The Known Unknowns of the Immune Response to Coccidioides

Abstract

Coccidioidomycosis, otherwise known as Valley Fever, is caused by the dimorphic fungi Coccidioides immitis and C. posadasii. While most clinical cases present with self-limiting pulmonary infection, dissemination of Coccidioides spp. results in prolonged treatment and portends higher mortality rates. While the structure, genome, and niches for Coccidioides have provided some insight into the pathogenesis of disease, the underlying immunological mechanisms of clearance or inability to contain the infection in the lung are poorly understood. This review focuses on the known innate and adaptive immune responses to Coccidioides and highlights three important areas of uncertainty and potential approaches to address them. Closing these gaps in knowledge may enable new preventative and therapeutic strategies to be pursued.

The Host Response to Coccidioidomycosis

“…Pulmonary epithelial cells interact with the arthroconidia very early in the course of infection. There have been some fascinating hypotheses about the importance of this interaction, but no data have been published [ 12 ]. Recently, Hsu reported that mutations in Duox1, a lung epithelial cell oxidase that generates H 2 O 2 , were more common in patients with disseminated coccidioidomycosis than in the general population, suggesting that this enzyme plays a role in innate resistance to coccidioidomycosis [ 13 ].…”

T cell responses to control fungal infection in an immunological memory lens

“…Coccidioidomycosis or Valley Fever is caused by species of dimorphic fungus, Coccidioides , a major cause of mycosis endemic to the southwestern United States. Immunity to Valley Fever is primarily associated with T cells expressing both type 1 and type 17 cytokines (Th1/Th17) ( 179 , 180 ). The regulatory T cells were associated with persistent coccidioidomycosis in the pediatric population that was recapitulated in resistant vs. susceptible mice ( 181 , 182 ).…”

The role of IL‐1β during human immunodeficiency virus type 1 infection

“…The latter includes for example, viral infections with: adenoviruses “in immunocompetent individuals” 4 ; dengue virus 5 ; hepatitis E virus 6 ; herpes simplex virus type 1 in “the acute infection state but not the latent infection state” 7 ; human papilloma virus 8 ; and West Nile virus 9 . Furthermore, it also includes bacterial infection with Coxiella burnetii in animals, 10 fungal infection with Coccidioides immitis and C. posadasii , 11 and parasitic infection with the protozoan Giardia duodenalis 12 …”

“…virus. 9 Furthermore, it also includes bacterial infection with Coxiella burnetii in animals, 10 fungal infection with Coccidioides immitis and C. posadasii, 11 and parasitic infection with the protozoan Giardia duodenalis. 12 As a matter of fact, an aberrant and/or dysfunctional/defective innate immune response during the early phases of an infection or upon encountering unwanted foreign particles/substances may be the leading cause of disease severity.…”