Dimorphism and Dissemination of Histoplasma capsulatum in the Upper Respiratory Tract after Intranasal Infection of Bats and Mice with Mycelial Propagules

Abstract

. This article describes, for the first time, the role of the nasal mucosa (NM) as the initial site for the Histoplasma capsulatum mycelial-to-yeast transition. The results highlight that yeasts may arrive to the cervical lymph nodes (CLN) via phagocytes. Bats and mice were intranasally infected with H. capsulatum mycelial propagules and they were killed 10, 20, and 40 minutes and 1, 2, and 3 hours after infection. The NM and the CLN were monitored for fungal presence . Yeasts compatible with H. capsulatum were detected within the NM and the CLN dendritic cells (DCs) 2–3 hours postinfection, using immunohistochemistry. Histoplasma capsulatum was re-isolated by culturing at 28°C from the CLN of both mammalian hosts 2–3 hours postinfection. Reverse transcription-polymerase chain reaction assays were designed to identify fungal dimorphism, using mycelial-specific ( MS8 ) and yeast-specific ( YPS3 ) gene expression. This strategy supported fast fungal dimorphism in vivo, which began in the NM 1 hour postinfection (a time point when MS8 and YPS3 genes were expressed) and it was completed at 3 hours (a time point when only the YPS3 transcripts were detected) in both bats and mice. The presence of intracellular yeasts in the nasal-associated lymphoid tissue (NALT), in the NM nonassociated with the NALT, and within the interdigitating DCs of the CLN suggests early fungal dissemination via the lymph vessels.

Histoplasma capsulatum Isolated from Tadarida brasiliensis Bats Captured in Mexico Form a Sister Group to North American Class 2 Clade

“…Bats are able to develop natural and experimental histoplasmosis infections [ 1 , 2 , 3 , 4 , 5 , 6 ]. Infected bats could act as reservoirs and dispersers of H. capsulatum in favorable environments, playing a possible role in the incorporation of the fungus in new ecological niches [ 7 , 8 , 9 ].…”

Unusual Differences in the Pulmonary Histopathology of Mice after Intranasal Infection with Mycelial Propagules of Histoplasma capsulatum Strains Classified as LAm A2 and NAm 2 Phylogenetic Species

“…Thus, by utilizing this innovative genetic approach and by simulating a natural host infection, these authors found relevant data, which undoubtedly demonstrated that infective Histoplasma M-phase propagules spent 2-3 h to convert in the parasitic Y-phase. Furthermore, they also demonstrated that this fungus can also utilize other extrapulmonary sites to initiate its M-to-Y transition, where the link between innate and adaptive immune responses occurs, such as the mucosal-associated lymphoid tissues in the upper respiratory tract [8].…”

“…A few studies have processed the infective M-phase to explore the immune responses triggered by the host to this particular fungal morphotype, in the clinical evolution of histoplasmosis. New information regarding different sites and the time spent for the in vivo H. capsulatum M-to-Y transition was reported by Suárez-Álvarez et al [8]. They detected the expression of phase-specific genes for M-and Y-phases using RT-PCR assays in tissue samples taken from the upper respiratory tract of infected mice.…”

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

“…Conidia and small hyphal fragments of the H. capsulatum mycelial phase constitute the major aerosolized infectious propagules found in the environment, which can be inhaled by susceptible hosts. Once in the host’s respiratory compartments are at 37 °C, the mycelial propagules convert to the parasitic yeast phase in approximately 1–3 h [ 6 ]. This facilitates an infection that can lead to a localized pulmonary disease or to a disseminated disease.…”