Abstract
Paracoccidioidomycosis (PCM) is an endemic systemic mycosis in Latin America, with the highest prevalence in Brazil, Colombia, and Venezuela. Fungi of the Paracoccidioides genus are etiologic agents of the disease. The 15 amino acid peptide P10 is derived from gp43, the main diagnostic antigen of Paracoccidioides brasiliensis. We previously reported that P10-pulsed dendritic cells (DCs) induce a protective response against P. brasiliensis. Presently, dexamethasone-treated BALB/c mice were intratracheally infected with P. brasiliensis Pb18 to establish the therapeutic efficacy of P10-pulsed DCs. Immunosuppressed and infected animals that received DCs had a reduction in their fungal burden, and this result was most pronounced in mice receiving DCs primed with P10. The efficacy of therapeutic DCs was significantly augmented by concomitant treatment with trimethoprim-sulfamethoxazole. Additionally, primed-DCs with or without the antifungal drug induced a beneficial Th1-biased immune response and significantly reduced tissue damage. In conclusion, these studies with immunocompromised mice demonstrate that P10-pulsed DCs with or without concomitant antifungal drugs are potently effective in combating invasive PCM. These findings support further translational studies to validate the use of P10-primed DCs for PCM in immunocompetent and immunosuppressed hosts.
Highlights
Paracoccidioidomycosis (PCM), caused by thermally dimorphic fungi of the Paracoccidioides genus, is one of the most important systemic granulomatous diseases in Latin America (Taborda et al, 2015)
Our findings show that the administration of P10-primed dendritic cells (DCs) to dexamethasone suppressed mice infected with P. brasiliensis are therapeutic in the setting of compromised immunity
Standard therapeutic regimens are associated with significant toxicities, such as nephrotoxicity and hepatotoxicity, and intense therapy does not prevent the development of disease sequelae, such as pulmonary fibrosis or scarring (Shikanai-Yasuda et al, 2006; Bocca et al, 2013; Buccheri et al, 2015)
Summary
Paracoccidioidomycosis (PCM), caused by thermally dimorphic fungi of the Paracoccidioides genus, is one of the most important systemic granulomatous diseases in Latin America (Taborda et al, 2015). Acquisition of Paracoccidioides spp. follows the inhalation of conidia, which are deposited into the lower respiratory tract. These propagules subsequently undergo morphogenic transformation into yeast forms, which constitute the pathogenic morphology in tissues (Taborda et al, 2015). Within weeks to months after initial infection, young adults often develop the acute or subacute forms of disease, and these are typically aggressive and require immediate antifungal treatment (Bocca et al, 2013). The chronic form of PCM is manifested months or years after infection, and disease varies in severity, this form can be as aggressive as the acute form (Bocca et al, 2013)
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