Paracoccidioides brasiliensis induces cytokine secretion in epithelial cells in a protease-activated receptor-dependent (PAR) manner

Oliveira, Priscila de; Juliano, María A.; Tanaka, Aparecida S.; Carmona, Adriana K.; Santos, Saara Maria Batista dos; Barros, Bianca Carla Silva Campitelli; Maza, Paloma Korehisa; Puccia, Rosana; Suzuki, Érika

doi:10.1007/s00430-016-0490-x

Cited by 10 publications

(8 citation statements)

References 24 publications

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“…A modified peptide derived from this molecule has been designed as a vaccine to prevent disease. (46,47) In our study, the gp43 gene showed the highest expression after macrophage infection with the Pb18 Y form. Considering that macrophages are fundamental in controlling fungal infections, the gp43 gene may be involved in a fungal evasion mechanism.…”

Section: Discussionsupporting

confidence: 51%

Gene expression of Paracoccidioides virulence factors after interaction with macrophages and fibroblasts

Braz

Sardi

Pitangui

et al. 2021

Mem. Inst. Oswaldo Cruz

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BACKGROUND Paracoccidioidomycosis (PCM) is a systemic mycosis with high prevalence in Latin America that is caused by thermodimorphic fungal species of the Paracoccidioides genus.OBJECTIVES In this study, we used quantitative polymerase chain reaction (qPCR) to investigate the expression of genes related to the virulence of Paracoccidioides brasiliensis (Pb18) and P. lutzii (Pb01) strains in their mycelial (M) and yeast (Y) forms after contact with alveolar macrophages (AMJ2-C11 cell line) and fibroblasts (MRC-5 cell line).METHODS The selected genes were those coding for 43 kDa glycoprotein (gp43), enolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 14-3-3 protein (30 kDa), phospholipase, and aspartyl protease. FINDINGS In the Pb18 M form, the aspartyl protease gene showed the highest expression among all genes tested, both before and after infection of host cells. In the Pb18 Y form after macrophage infection, the 14-3-3 gene showed the highest expression among all genes tested, followed by the phospholipase and gp43 genes, and their expression was 50-fold, 10-fold, and 6-fold higher, respectively, than that in the M form. After fibroblast infection with the Pb18 Y form, the 14-3-3 gene showed the highest expression, followed by the phospholipase and aspartyl protease genes, and their expression was 25-fold, 10-fold, and 10-fold higher, respectively, than that in the M form. Enolase and aspartyl protease genes were expressed upon infection of both cell lines. After macrophage infection with the Pb01 Y form, the 14-3-3 gene showed the highest expression, followed by the phospholipase and aspartyl protease genes, and their expression was 18-fold, 12.5-fold, and 6-fold higher, respectively, than that in the M form. MAIN CONCLUSIONSIn conclusion, the data show that the expression of the genes analysed may be upregulated upon fungushost interaction. Therefore, these genes may be involved in the pathogenesis of paracoccidioidomycosis.

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Section: Discussionsupporting

confidence: 51%

Gene expression of Paracoccidioides virulence factors after interaction with macrophages and fibroblasts

Braz

Sardi

Pitangui

et al. 2021

Mem. Inst. Oswaldo Cruz

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“…As P. brasiliensis secretes compounds that may promote different effects in the host 11,12 , we verified if the decrease of α3 integrin levels in A549 cells after 24 h could be a result of this fungal secretion. For this, A549 cells were cultured in 6-well plates, and P. brasiliensis yeasts were placed in the upper compartment of Transwell platforms or in direct contact with the epithelial cells.…”

Section: Tlr2 Expression Levels In Lung Epithelial Cells Infected Witmentioning

confidence: 88%

“…Over the past years, our research group has focused on studying the lung epithelial cell responses to fungal infections, especially regarding the mechanisms involved in the release of inflammatory cytokines induced by yeasts of Paracoccidioides or Histoplasma capsulatum [7][8][9][10][11][12][13] . Our data have demonstrated that different fungal species promote cytokine secretion in lung epithelial cell in distinct manners.…”

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confidence: 99%

Paracoccidioides brasiliensis downmodulates α3 integrin levels in human lung epithelial cells in a TLR2-dependent manner

Barros

Almeida

Suzuki

2020

Sci Rep

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Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America and may be caused by the species Paracoccidioides brasiliensis. In the lungs, this fungus interacts with epithelial cells, activating host cell signalling pathways, resulting in the production of inflammatory mediators. This event may be initiated through the activation of Pattern-Recognition Receptors such as Toll-like Receptors (TLRs). By interacting with cell wall components, TLR2 is frequently related to fungal infections. In this work, we show that, after 24 h post-infection with P. brasiliensis, A549 lung epithelial cells presented higher TLR2 levels, which is important for IL-8 secretion. Besides, integrins may also participate in pathogen recognition by host cells. We verified that P. brasiliensis increased α3 integrin levels in A549 cells after 5 h of infection and promoted interaction between this receptor and TLR2. However, after 24 h, surprisingly, we verified a decrease of α3 integrin levels, which was dependent on direct contact between fungi and epithelial cells. Likewise, we observed that TLR2 is important to downmodulate α3 integrin levels after 24 h of infection. Thus, P. brasiliensis can modulate the host inflammatory response by exploiting host cell receptors and cell signalling pathways.

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“…P. brasiliensis showed 53 ORFs encoding proteases, including proteasome subunits, aspartyl, cysteine, metallo-, and serine proteases [102]. However, only a few Paracoccidioides proteases have been characterized over the last two decades; these proteases include serine protease and aspartyl proteases (PbSap) [103][104][105][106]. PbSap is a secreted protease that has been reported in culture supernatants [103,104], and its expression increased in the highly virulent isolate Pb18 and decreased after several generations in culture [104].…”

Section: Infection and Evasion Mechanismsmentioning

confidence: 99%

Updates in Paracoccidioides Biology and Genetic Advances in Fungus Manipulation

Chaves

Navarro

Barros

et al. 2021

JoF

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The dimorphic fungi of the Paracoccidioides genus are the causative agents of paracoccidioidomycosis (PCM). This disease is endemic in Latin America and primarily affects workers in rural areas. PCM is considered a neglected disease, despite being a disabling disease that has a notable impact on the public health system. Paracoccidioides spp. are thermally dimorphic fungi that present infective mycelia at 25 °C and differentiate into pathogenic yeast forms at 37 °C. This transition involves a series of morphological, structural, and metabolic changes which are essential for their survival inside hosts. As a pathogen, the fungus is subjected to several varieties of stress conditions, including the host immune response, which involves the production of reactive nitrogen and oxygen species, thermal stress due to temperature changes during the transition, pH alterations within phagolysosomes, and hypoxia inside granulomas. Over the years, studies focusing on understanding the establishment and development of PCM have been conducted with several limitations due to the low effectiveness of strategies for the genetic manipulation of Paracoccidioides spp. This review describes the most relevant biological features of Paracoccidioides spp., including aspects of the phylogeny, ecology, stress response, infection, and evasion mechanisms of the fungus. We also discuss the genetic aspects and difficulties of fungal manipulation, and, finally, describe the advances in molecular biology that may be employed in molecular research on this fungus in the future.

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Paracoccidioides brasiliensis induces cytokine secretion in epithelial cells in a protease-activated receptor-dependent (PAR) manner

Cited by 10 publications

References 24 publications

Gene expression of Paracoccidioides virulence factors after interaction with macrophages and fibroblasts

Gene expression of Paracoccidioides virulence factors after interaction with macrophages and fibroblasts

Paracoccidioides brasiliensis downmodulates α3 integrin levels in human lung epithelial cells in a TLR2-dependent manner

Updates in Paracoccidioides Biology and Genetic Advances in Fungus Manipulation

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