Histoplasma Capsulatum: Mechanisms for Pathogenesis

Abstract

Histoplasmosis, caused by the dimorphic environmental fungus Histoplasma capsulatum, is a major mycosis on the global stage. Acquisition of the fungus by mammalian hosts can be clinically silent or it can lead to life-threatening systemic disease, which can occur in immunologically intact or deficient hosts, albeit severe disease is more likely in the setting of compromised cellular immunity. H. capsulatum yeast cells are highly adapted to the mammalian host as they can effectively survive within intracellular niches in select phagocytic cells. Understanding the biological response by both the host and H. capsulatum will facilitate improved approaches to prevent and/or modify disease. This review presents our current understanding of the major pathogenic mechanisms involved in histoplasmosis.

Biofilm Formation by Histoplasma capsulatum in Different Culture Media and Oxygen Atmospheres

“…Histoplasmosis is a systemic mycosis widely distributed worldwide with high prevalence in America ( Mittal et al, 2019 ). Most cases are reported in Ohio and Mississippi River valleys in the United States, Mexico, Brazil, and some regions of Guyana (Guyana Shield).…”

Differential miRNA Expression in Human Macrophage-Like Cells Infected with Histoplasma capsulatum Yeasts Cultured in Planktonic and Biofilm Forms

“…This facilitates an infection that can lead to a localized pulmonary disease or to a disseminated disease. Indeed, it is known that the transition from the mycelial phase to the parasitic yeast phase is required for H. capsulatum pathogenicity, and that the virulence of the fungal strains is associated with genes that are only expressed in the yeast phase [ 7 , 8 , 9 , 10 , 11 ].…”

Immunoproteomics Reveals Pathogen’s Antigens Involved in Homo sapiens–Histoplasma capsulatum Interaction and Specific Linear B-Cell Epitopes in Histoplasmosis

“…The yeast cells of H. capsulatum are highly adapted to the host since they can survive and reproduce within phagocytic cells (Garfoot and Rappleye, 2016). Histoplasma capsulatum strategies against macrophages include evasion from the immune response on entry, inactivation of nitrogen and oxygen reactive species, prevention of phagolysosomal fusion, hindrance of lysosomal pH reduction, siderophore production, and induction of apoptosis for escape and dissemination into the host (Long et al, 2003;Missall et al, 2004;Guimarães et al, 2011;Hilty et al, 2011;Mittal et al, 2019).…”

“…The infection by H. capsulatum depends on a complex interaction between the fungus and the mammalian host, with disease prognosis determined by factors such as immune status of the host, strain virulence, and inhaled fungal burden ( Sepúlveda et al., 2014 ). Although histoplasmosis affects either immunologically intact or deficient hosts, individuals with compromised cellular immune response presents more severe manifestations of this disease ( Mittal et al., 2019 ). The yeast cells of H. capsulatum are highly adapted to the host since they can survive and reproduce within phagocytic cells ( Garfoot and Rappleye, 2016 ).…”