Pathogenicity and Growth Conditions Modulate Fonsecaea Extracellular Vesicles’ Ability to Interact With Macrophages

Abstract

Chromoblastomycosis (CBM) is a chronic cutaneous and subcutaneous mycosis caused by black, dimorphic, and filamentous fungi of the Herpothrichiellaceae family, such as species of the genus Fonsecaea. These fungi can switch between the saprophytic forms (conidia and hyphae) and the pathogenic form, the muriform cells (MCs), which is considered an essential mechanism for fungal virulence. Nearly all types of cells can produce membranous structures formed by a lipid bilayer that communicate extracellularly with other cells, known as “extracellular vesicles” (EVs), which may act as virulence factors, as observed for several species of pathogenic fungi. Our findings demonstrated for the first time that F. pedrosoi, F. nubica, and F. erecta produce EVs in response to nutritional conditions. The EVs varied in sterol and protein contents, size, and morphology. Moreover, the EVs induced different cytokine and nitric oxide release patterns by bone marrow-derived macrophages (BMDMs). The EVs activated IL-1β production, possibly acting as the first signal in inflammasome activation. Unlike the pathogenic species, the EVs isolated from F. erecta did not significantly stimulate TNF and IL-10 production in general. Overall, these results demonstrated that different species of Fonsecaea produce EVs capable of modulating pro- and anti-inflammatory cytokine and nitric oxide production by BMDMs and that growth conditions affected the immunomodulatory capacities of the EVs as well as their size, content, and morphology.

Fungi extracellular vesicles: extraction, cargo, and the immune system response

“…(Ikeda et al, 2018). In the upcoming years, EVs were isolated from other pathogenic genera such as Aspergillus (Souza et al, 2019;Brauer et al, 2020), Pichia (Leone et al, 2017), Rhizopus (Liu et al, 2018), Trichophyton (Bittencourt et al, 2018, Exophiala (Lavrin et al, 2020) and Fonsecaea (Las-Casas et al, 2022). Also, EVs were found in some phytopathogens such as Alternaria infectoria (Silva et al, 2014), Fusarium oxysporum sp.…”

“…In mycology, we have works demonstrating the ability of fungal EVs to interact with the host immune system (Table 1), as seen in A. flavus (Brauer et al, 2020), A. fumigatus (Souza et al, 2019;Freitas et al, 2023), C. albicans (Vargas et al, 2015;Wolf et al, 2015;Vargas et al, 2021;Honorato et al, 2022;Wei et al, 2023), C. auris , C. haemulonii var. vulnera , C. glabrata, C. parapsilosis, C. tropicalis (Kulig et al, 2022), C. deuterogatti (Castelli et al, 2022); C. gatti (Bielska et al, 2018), C. neoformans (Oliveira et al, 2010, Huang et al, 2012Colombo et al, 2019;Marina et al, 2020;Rizzo et al, 2021), F. pedrosoi, F. nubica (Las-Casas et al, 2022), H. capsulatum (Baltazar et al, 2018), M. sympodialis (Gehrmann et al, 2011), P. brasiliensis (Peres da Baltazar et al, 2021;Octaviano et al, 2022), S. brasiliensis (Ikeda et al, 2018;Campos et al, 2021), T. marneffei (Yang et al, 2021) and T. interdigitale (Bitencourt et al, 2018).…”

Involvement of GPR43 Receptor in Effect of Lacticaseibacillus rhamnosus on Murine Steroid Resistant Chronic Obstructive Pulmonary Disease: Relevance to Pro-Inflammatory Mediators and Oxidative Stress in Human Macrophages

“…Despite the involvement of neutrophils in resistance to corticosteroid treatment in individuals with COPD, innate immunity cells such as macrophages play a pivotal role in both the initial and later phases of the inflammatory response in COPD [13]. Their activation is intricately controlled by the immune response to pathogens or tissue damage [14,15]. Consequently, when exposed to harmful particles, macrophages can become activated, leading to the secretion of elevated levels of pro-inflammatory cytokines.…”

Expanding the Toolbox for Functional Genomics in Fonsecaea pedrosoi: The Use of Split-Marker and Biolistic Transformation for Inactivation of Tryptophan Synthase (trpB) Gene

“…Inside infected tissue, this pathogen is able to differentiate into sclerotic cells, which are large, spherical, highly pigmented, thick-walled, and resistant to immune response [ 1 , 30 , 31 , 32 , 33 ]. The dimorphic transition is probably the main morphogenetic event required for CBM; the molecular mechanism and host factors that promote cell differentiation are not yet clear [ 1 , 34 ].…”