Pathogenesis of Coccidioidomycosis

Abstract

Coccidioidomycosis is a systemic fungal infection endemic to the American Southwest, caused by Coccidioides immitis and Coccidioides posadasii. The infection has a wide variety of clinical manifestations in humans, from asymptomatic infection to severe disease. Infection occurs through inhalation of fungal spores, leading to primary pulmonary infection and occasionally to hematogenous dissemination to other sites. Both fungal and host factors contribute to pathogenesis of this infection. Cellular and innate immune responses are involved in the protective response in both humans and mice. This review summarizes recent research on microbial and host factors involved in the pathogenesis of coccidioidomycosis.

Pathology of coccidioidomycosis in llamas and alpacas

“…The most common mechanism of infection is by inhalation of arthroconidia, but direct inoculation of these structures through the skin occurs occasionally, causing cutaneous lesions that usually do not progress to systemic infection. 1,13 Following inhalation and deposition within the lung, the arthroconidia transform into yeast forms that can be phagocytized by neutrophils and macrophages, within which they rapidly transition into immature spherules. 3 The latter are 10-20 µm diameter; when mature, spherules are typically 20-200 µm diameter and develop numerous 2-5 µm endospores.…”

Pulmonary Coccidioidomycosis

“…The presence of spherules and endospores in tissue triggers a further local immune response. 31 Spherules, in particular, react with complement and promote chemotaxis of more PMNs and eosinophils. 32 When spherules burst and release endospores, PMNs and macrophages engulf the endospores.…”

Early Events in Coccidioidomycosis

“…As Mead and others wrote in 2018, "the molecular mechanisms that initiate the morphological switch from a saprobic to a parasitic phase are not understood" (29). The obstacles to understanding these mechanisms include (i) applying in vitro models to in vivo processes, (ii) limitations of applying animal models (primarily murine) to the human disease process (14), (iii) difficulties in studying the early infective process in humans (30), and (iv) the risk of attempting to ascribe biological processes studied in other fungi to Coccidioides.…”

“…This may interfere with the assessment of early immune system responses that lead to disease control in humans. In addition, unlike humans, a low inoculum intranasally leads to rapid death (14). There are no studies correlating the inoculum size with disease severity in humans.…”

“…Humoral factors, such as complement, could be part of the initial host interactions. Histopathological changes are well documented in the murine model, but early histological changes in the human lung are not well understood (14). Pathogen-related factors that aid in inhalation, adhesion, invasion, and survival in the host have been studied, but there are many areas still to be investigated (15).…”