Fonsecaeapedrosoi Conidia and Hyphae Activate Neutrophils Distinctly: Requirement of TLR-2 and TLR-4 in Neutrophil Effector Functions

Breda, Leandro Carvalho Dantas; Breda, Cristiane Naffah de Souza; Almeida, José Roberto Fogaça de; Paulo, Larissa Neves Monteiro; Jannuzzi, Grasielle Pereira; Menezes, Isabela de Godoy; Albuquerque, Renata Chaves; Câmara, Niels Olsen Saraiva; Ferreira, Karen Spadari; Almeida, Sandro Rogério de

doi:10.3389/fimmu.2020.540064

Cited by 12 publications

(16 citation statements)

References 75 publications

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“…Confirming the in vitro findings, TLR-2KO, TLR-4KO, and Myd88-KO animals infected with F. pedrosoi conidia showed poor prognoses compared with wild-type animals, demonstrating that the TLRs are an essential class of PRRs for the recognition and control of CBM agents [ 47 , 113 ]. Although fungal recognition by TLRs has proved to be important in the early stages of the disease, it seems that F. pedrosoi has the ability to hide from the host’s immune system.…”

Section: Immune Response In Cbmmentioning

confidence: 72%

“…We believe that the different membranes and cell wall components may influence the host–pathogen interactions; however, how these specific components interact with the host immune system is still unclear. Our recent study demonstrated that TLR-2 is essential for conidia killing by neutrophils, but not for hyphae killing [ 47 ]. However, TLR-2 is known to interact with beta-glucan, a component expressed in the two morphotypes of F. pedrosoi .…”

Section: Fonsecaea Pedrosoi Cell Wallmentioning

confidence: 99%

“…Therefore, although the levels of IFN-γ are related to a mild form of the disease, the mechanism of IFN-γ to act against CBM agents is still unclear. Unlike macrophages, neutrophils show a high in vitro microbicidal activity against F. pedrosoi [ 47 , 96 ]. In 2011, in an analysis of skin biopsies from mice infected with three different forms of F. pedrosoi (conidia, sclerotic bodies, and hyphae), Machado and colleagues observed dead fragments or injured fungal particles in neutrophilic areas, while intact or particles similar to the live particles were observed in regions of macrophage cells.…”

Section: Immune Response In Cbmmentioning

confidence: 99%

“…Recently, our group demonstrated that neutrophils kill conidia and hyphae in vitro in a distinct manner. Whilst conidia killing relies on phagocytosis and ROS production, neutrophils kill hyphae particles through ROS-independent Neutrophil Extracellular Trap (NET) release [ 47 ]. These findings, together with the increase of IL-17 in skin lesions of CBM patients, suggest that neutrophil attraction and activation are the most important roles of IL-17 in CBM infection, leading to F. pedrosoi killing and avoiding the spread of the disease.…”

Section: Immune Response In Cbmmentioning

confidence: 99%

“…A recent study showed an increase in tlr-2 and tlr-4 gene expression by macrophages infected with F. pedrosoi sclerotic bodies, but not with conidia. Later, our group demonstrated that TLR-2 and TLR-4 are essential receptors for F. pedrosoi conidia recognition and killing by murine neutrophils [ 47 ] ( Figure 3 ). Although these receptors are important for conidia phagocytosis and ROS production, they are dispensable for hyphae killing through NET release.…”

Section: Immune Response In Cbmmentioning

confidence: 99%

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Immune Sensing and Potential Immunotherapeutic Approaches to Control Chromoblastomycosis

Breda

Menezes

Paulo

et al. 2020

JoF

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Chromoblastomycosis (CBM) is a neglected, chronic, and progressive subcutaneous mycosis caused by different species of fungi from the Herpotrichiellaceae family. CBM disease is usually associated with agricultural activities, and its infection is characterized by verrucous, erythematous papules, and atrophic lesions on the upper and lower limbs, leading to social stigma and impacts on patients’ welfare. The economic aspect of disease treatment is another relevant issue. There is no specific treatment for CBM, and different anti-fungal drug associations are used to treat the patients. However, the long period of the disease and the high cost of the treatment lead to treatment interruption and, consequently, relapse of the disease. In previous years, great progress had been made in the comprehension of the CBM pathophysiology. In this review, we discuss the differences in the cell wall composition of conidia, hyphae, and muriform cells, with a particular focus on the activation of the host immune response. We also highlight the importance of studies about the host skin immunology in CBM. Finally, we explore different immunotherapeutic studies, highlighting the importance of these approaches for future treatment strategies for CBM.

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Section: Immune Response In Cbmmentioning

confidence: 72%

Section: Fonsecaea Pedrosoi Cell Wallmentioning

confidence: 99%

Section: Immune Response In Cbmmentioning

confidence: 99%

Section: Immune Response In Cbmmentioning

confidence: 99%

Section: Immune Response In Cbmmentioning

confidence: 99%

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Immune Sensing and Potential Immunotherapeutic Approaches to Control Chromoblastomycosis

Breda

Menezes

Paulo

et al. 2020

JoF

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The origin of human pathogenicity and biological interactions in Chaetothyriales

et al. 2023

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Fungi in the order Chaetothyriales are renowned for their ability to cause human infections. Nevertheless, they are not regarded as primary pathogens, but rather as opportunists with a natural habitat in the environment. Extremotolerance is a major trend in the order, but quite different from black yeasts in Capnodiales which focus on endurance, an important additional parameter is advancing toxin management. In the ancestral ecology of rock colonization, the association with metabolite-producing lichens is significant. Ant-association, dealing with pheromones and repellents, is another mainstay in the order. The phylogenetically derived family, Herpotrichiellaceae, shows dual ecology in monoaromatic hydrocarbon assimilation and the ability to cause disease in humans and cold-blooded vertebrates. In this study, data on ecology, phylogeny, and genomics were collected and analyzed in order to support this hypothesis on the evolutionary route of the species of Chaetothyriales. Comparing the ribosomal tree with that of enzymes involved in toluene degradation, a significant expansion of cytochromes is observed and the toluene catabolism is found to be complete in some of the Herpotrichiellaceae. This might enhance human systemic infection. However, since most species have to be traumatically inoculated in order to cause disease, their invasive potential is categorized as opportunism. Only in chromoblastomycosis, true pathogenicity might be surmised. The criterion would be the possible escape of agents of vertebrate disease from the host, enabling dispersal of adapted genotypes to subsequent generations.

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Neutrophil-suppressive activity over T-cell proliferation and fungal clearance in a murine model of Fonsecaea pedrosoi infection

Breda

Kaihami

et al. 2021

Sci Rep

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Neutrophils are essential to control several fungal infections. These cells are commonly known for their pro-inflammatory activities. However, some studies have demonstrated the anti-inflammatory properties of neutrophils during certain infectious diseases, culminating in the inhibition of T cell proliferation. Chromoblastomycosis (CBM) is a deep and progressive mycosis that affects thousands of people worldwide. Although neutrophil infiltrates are observed in the lesion histopathology, the fungus can overtake the immune system response and destroy the host-infected tissue. The present study demonstrated that neutropenic animals had an increase in the IL-6 production in the spleen and liver, followed by a lower fungal burden in these organs up to 14 days of infection. Neutropenic animals also showed a lower F. pedrosoi-specific antibody production 14-days post infection and higher T-cell proliferation in the in vitro experiments after stimulation with F. pedrosoi-purified proteins. Taken together, our results suggest that the presence of regulatory neutrophils in the mouse model of F. pedrosoi infection could act favoring the spread of the fungus and the chronicity of the infection. These findings shed light on the CBM treatment, which might target neutrophil polarization as a new therapy approach to treat CBM lesions.

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Fonsecaeapedrosoi Conidia and Hyphae Activate Neutrophils Distinctly: Requirement of TLR-2 and TLR-4 in Neutrophil Effector Functions

Cited by 12 publications

References 75 publications

Immune Sensing and Potential Immunotherapeutic Approaches to Control Chromoblastomycosis

Immune Sensing and Potential Immunotherapeutic Approaches to Control Chromoblastomycosis

The origin of human pathogenicity and biological interactions in Chaetothyriales

Neutrophil-suppressive activity over T-cell proliferation and fungal clearance in a murine model of Fonsecaea pedrosoi infection

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