Host Response to Coccidioides Infection: Fungal Immunity

Abstract

Coccidioidomycosis is a fungal, respiratory disease caused by Coccidioides immitis and Coccidioides posadasii . This emerging infectious disease ranges from asymptomatic to pulmonary disease and disseminated infection. Most infections are cleared with little to no medical intervention whereas chronic disease often requires life-long medication with severe impairment in quality of life. It is unclear what differentiates hosts immunity resulting in disease resolution versus chronic infection. Current understanding in mycology-immunology suggests that chronic infection could be due to maladaptive immune responses. Immunosuppressed patients develop more severe disease and mouse studies show adaptive Th1 and Th17 responses are required for clearance. This is supported by heightened immunosuppressive regulatory responses and lowered anti-fungal T helper responses in chronic Coccidioides patients. Diagnosis and prognosis is difficult as symptoms are broad and overlapping with community acquired pneumonia, often resulting in misdiagnosis and delayed treatment. Furthermore, we lack clear biomarkers of disease severity which could aid prognosis for more effective healthcare. As the endemic region grows and population increases in endemic areas, the need to understand Coccidioides infection is becoming urgent. There is a growing effort to identify fungal virulence factors and host immune components that influence fungal immunity and relate these to patient disease outcome and treatment. This review compiles the known immune responses to Coccidioides spp. infection and various related fungal pathogens to provide speculation on Coccidioides immunity.

A Review of Coccidioides Research, Outstanding Questions in the Field, and Contributions by Women Scientists

“…The progress of vaccine and immunology research in the Coccidioides field is largely thanks to the women researchers in the field. There are some excellent women-led review articles highlighting the recent advances in the immune response, host-pathogen interactions, and development of a Coccidioides vaccine [ 95 •, 96 – 98 , 99 •]. In this section, we will discuss briefly what is known about the host immune response to Coccidioides and the development of a vaccine to combat coccidioidomycosis.…”

B Cell Chronic Lymphocytic Leukemia Development in Mice with Chronic Lung Exposure toCoccidioidesFungal Arthroconidia

“…Coccidioides infections are known to elicit both inflammatory and counteracting anti-inflammatory cell populations ( 60 ), but the plasticity of the myeloid lineage is little understood ( 61 , 62 ). Because nonclassical (patrolling or anti-inflammatory) monocytes/macrophages (M2 cells) are reported to play a key role in B-CLL development ( 63 , 64 ), we examined both nonclassical M2 monocytes and classical M1 monocytes within blood samples from the experiment’s cohorts.…”

Histoplasma capsulatum Activates Hematopoietic Stem Cells and Their Progenitors through a Mechanism Dependent on TLR2, TLR4, and Dectin-1

“…Arg-1 converts L-arginine to L-ornithine, which is a polyamine used for the cell proliferation of pathogenic dimorphic fungi such as Coccidioides spp. [ 30 , 31 ]. In this sense, although the fungus induces the expression of iNOS, it also induces the expression of Arg-1: thus, two antagonistic enzymes could be directly related to the findings.…”