<scp>M</scp>2 macrophages and inflammatory cells in oral lesions of chronic paracoccidioidomycosis

Carli, Marina Lara de; Miyazawa, Marta; Nonogaki, Suely; Shirata, Neuza Kasumi; Oliveira, Denise Tostes; Pereira, Alessandro Antônio Costa; Hanemann, João Adolfo Costa

doi:10.1111/jop.12333

Cited by 16 publications

(17 citation statements)

References 45 publications

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“…Notably, a recent study has demonstrated that Candida albicans chitin can induce polarization of human macrophage towards M2 phenotype with increased arginase-1 activity [ 30 ]. It is well established that the anti-inflammatory cytokines secreted by human or mice M2 macrophages contribute to the impairment of Th1 cell development [ 31 , 32 ]. Therefore, we hypothesize that chitin accumulation on the outer cell wall of F .…”

Section: Introductionmentioning

confidence: 99%

Transformation of Fonsecaea pedrosoi into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN-γ production

Dong¹,

Tong²,

et al. 2018

PLoS Negl Trop Dis

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Fonsecaea pedrosoi (F. pedrosoi) is the most common agent of chromoblastomycosis. Transformation of this fungus from its saprophytic phase into pathogenic sclerotic cells in tissue is an essential link to the refractoriness of this infection. Experimental studies in murine models have shown that the absence of CD4+ T cells impairs host defense against F. pedrosoi infection. Clinical research has also suggested that a relatively low level of the Th1 cytokine INF-γ and inefficient T cell proliferation are simultaneously present in patients with severe chromoblastomycosis upon in vitro stimulation with ChromoAg, an antigen prepared from F. pedrosoi. In the present study, we show that in mice intraperitoneally infected with F. pedrosoi-spores, -hyphae or in vitro-induced sclerotic cells respectively, the transformation of this causative agent into sclerotic cells contributes to a compromised Th1 cytokine production in the earlier stage of infection with impaired generation of neutrophil reactive oxygen species (ROS) and pan-inhibition of Th1/Th2/Th17 cytokine production with disseminated infection in the later stage by using a CBA murine Th1/Th2/Th17 cytokine kit. In addition, we have further demonstrated that intraperitoneal administration of recombinant mouse IFN-γ (rmIFN-γ) effectively reduces the fungal load in the infected mouse spleen, and dampens the peritoneal dissemination of F. pedrosoi-sclerotic cells. Meanwhile, exogeneous rmIFN-γ contributes to the formation and maintenance of micro-abscess and restores the decrease in neutrophil ROS generation in the mouse spleen infected with F. pedrosoi-sclerotic cells. Of note, we have once again demonstrated that it is a chitin-like component, but not β-glucans or mannose moiety, that exclusively accumulates on the outer cell wall of F. pedrosoi-sclerotic cells which were induced in vitro or isolated from the spleens of intraperitoneally infected BALB/c mice. In addition, our results indicate that decreased accumulation of chitin on the surface of live F. pedrosoi-sclerotic cells after chitinase treatment can be self-compensated in a time-dependent manner. Importantly, we have for the first time demonstrated that exclusive accumulation of chitin on the transformed sclerotic cells of F. pedrosoi is involved in an impaired murine Th1 cytokine profile, therefore promoting the refractoriness of experimental murine chromoblastomycosis.

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Section: Introductionmentioning

confidence: 99%

Transformation of Fonsecaea pedrosoi into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN-γ production

Dong¹,

Tong²,

et al. 2018

PLoS Negl Trop Dis

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“…However, capacity for EVs from P. brasiliensis to mediate immunomodulatory effects has not been investigated. A recent study showed that in chronic PCM the majority of macrophages are M2 30 , which contribute to the development of a Th2 immune response that is associated with susceptibility to the infection 30 31 . Therefore, we hypothesized that EVs from P. brasiliensis could play a determinant role in the interaction of the pathogen with macrophages and could modulate host immunity, as was reported for EVs from C. neoformans 15 .…”

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confidence: 99%

Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro

Silva

Roque-Barreira

Casadevall

et al. 2016

Sci Rep

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Extracellular vesicles (EVs) released by eukaryotes, archaea, and bacteria contain proteins, lipids, polysaccharides, and other molecules. The cargo analysis of EVs shows that they contain virulence factors suggesting a role in the pathogenesis of infection. The proteome, lipidome, RNA content, and carbohydrate composition of EVs from Paracoccidioides brasiliensis and Paracoccidioides lutzii were characterized. However, the effects of P. brasiliensis EVs on the host immune system have not yet been investigated. Herein, we verified that EVs from P. brasiliensis induce the production of proinflammatory mediators by murine macrophages in a dose-dependent manner. Addition of EV to macrophages also promoted transcription of the M1-polarization marker iNOs and diminish that of the M2 markers Arginase-1, Ym-1, and FIZZ-1. Furthermore, the augmented expression of M2-polarization markers, stimulated by IL-4 plus IL-10, was reverted toward an M1 phenotype in response to secondary stimulation with EVs from P. brasiliensis. The ability of EVs from P. brasiliensis to promote M1 polarization macrophages favoring an enhanced fungicidal activity, demonstrated by the decreased CFU recovery of internalized yeasts, with comparable phagocytic efficacy. Our results suggest that EVs from P. brasiliensis can modulate the innate immune response and affect the relationship between P. brasiliensis and host immune cells.

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“…PCM is a leading cause of death from chronic infectious in Brazil, affecting mainly rural workers with mean age of 47 years . Due to the absence of compulsory notification in our country, the accessibility of data about the oral manifestation of PCM is still limited .…”

Section: Discussionmentioning

confidence: 99%

“…PCM is a leading cause of death from chronic infectious in Brazil, affecting mainly rural workers with mean age of 47 years. 7,34 Due to the absence of compulsory notification in our country, the accessibility of data about the oral manifestation of PCM is still limited. 9,35 Interestingly, the oral manifestation of the chronic PCM does not occur in all patients 36 ; some authors reported oral involvement in 50% of cases, rising involvement of this site in agreement with patients' age.…”

Section: Discussionmentioning

confidence: 99%

“…The disease has primary pulmonary involvement and may spread to the skin, reticuloendothelial system, adrenal glands and oral mucosa . About 30% to 50% of the chronic PCM patients exhibit oral manifestations, characterised by erythematous granular ulcers with haemorrhagic dots that is called moriform stomatitis involving mainly hard and soft palate, buccal, labial and gingival mucosa, or severe periodontal bone loss . Oral PCM manifestations favour the recognition of the disease and make possible the diagnosis through incisional biopsy …”

Section: Introductionmentioning

confidence: 99%

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Different DNA methylation profile is demonstrated in paracoccidioidomycosis patients without oral lesions

Singi

Rocha

Carli

et al. 2019

Mycoses

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Summary Background Paracoccidioidomycosis (PCM) is a neglected fungal infection with a high impact on the quality of life of the affected patients. The disease presents primary pulmonary involvement and systemic dissemination may occur. About 50% of the cases show oral involvement, and the factors that lead to this manifestation are not clear. Objectives The aim of this study was to evaluate the DNA methylation profile in PCM patients with oral lesions. Material and Methods Genomic DNA was extracted from whole blood of eighteen PCM patients, being ten with oral lesions and eight with no oral lesion. Analysis of methylation profile was performed using the technique of methylation‐sensitive arbitrarily primed PCR (MS‐AP‐PCR). The sequences of recombinant plasmids obtained were evaluated according to parameters that define a CpG island, as well as their relative position in the known human genome genes and/or CpG islands. Results After DNA amplification, three different expressed bands were observed between the two groups, being found in the samples of patients with no oral manifestations. The cloned fragment in the plasmid showed similarity with a DNA sequence present in chromosome 20, next to the YTHDF1 gene. Other bands showed homology with intronic region in the genes RBPMS2 and DPH6 and no CpG island was identified. Conclusions DNA methylation was found in PCM patients with no oral lesion affecting the YTHDF1 gene. Further studies are necessary to elucidate to role of YTHDF1 gene in the oral PCM manifestations.

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M2 macrophages and inflammatory cells in oral lesions of chronic paracoccidioidomycosis

Abstract: M2-activated macrophages were the majority among inflammatory cells in chronic PCM, characterizing the action of a Th2-immune response. Nevertheless, Th1 cytokines were also found; mainly IL-1β, which was associated with fungi counting in oral lesions.

Cited by 16 publications

References 45 publications

Transformation of Fonsecaea pedrosoi into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN-γ production

Transformation of Fonsecaea pedrosoi into sclerotic cells links to the refractoriness of experimental chromoblastomycosis in BALB/c mice via a mechanism involving a chitin-induced impairment of IFN-γ production

Extracellular vesicles from Paracoccidioides brasiliensis induced M1 polarization in vitro

Different DNA methylation profile is demonstrated in paracoccidioidomycosis patients without oral lesions

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