Immune Sensing and Potential Immunotherapeutic Approaches to Control Chromoblastomycosis

Breda, Leandro Carvalho Dantas; Menezes, Isabela G.; Paulo, Larissa Neves Monteiro; Almeida, Sandro Rogério de

doi:10.3390/jof7010003

Cited by 9 publications

(32 citation statements)

References 125 publications

(166 reference statements)

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“…The innate immune response is very important in both chromoblastomycosis and leprosy [34][35][36]. In immunosenescence, dysfunction of innate immunity cells is observed, causing a decrease in phagocytosis, destruction of fungal elements and an increase in the immunomodulation produced by the etiological agents of leprosy, facilitating the progression of both diseases.…”

Section: Discussionmentioning

confidence: 99%

Chromoblastomycosis-Leprosy Co-Infection in Central West Brazil. Presentation of Three Cases and Literature Review

et al. 2022

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Chromoblastomycosis and leprosy are chronic diseases with high prevalence in tropical and subtropical regions. Brazil is one of the countries with the highest incidence and prevalence for both diseases, however, reports of co-infections are scarce. The aim of this study was to describe three cases of chromoblastomycosis-leprosy co-infection in patients from Mato Grosso state, Brazil. A review of chromoblastomycosis-leprosy co-infection was performed of English, Portuguese and Spanish publications in LILACS, SciELO, PubMed and Web of Science databases using the descriptors (chromoblastomycosis OR cromoblastomicose OR cromoblastomicosis) AND (leprosy OR hanseníase OR lepra), without time period delimitation. Nineteen cases were included, 16 cases were published in 11 articles, plus the three cases reported in the current study. Most reported coninfection cases came from Brazil. Majority of the patients were male with a mean age of 52.2 years. Farmer was the main occupational activity reported. In 12 patients, the clinical signs and symptoms of leprosy started first. No contacts with patients affected by leprosy, armadillos or history of injuries at the anatomical site of chromoblastomycosis lesions were reported. Five leprosy patients who received steroid treatment for leprosy reactions or neuropathies, were diagnosed with chromoblastomycosis during immunosuppressive therapy. Four cases (21.1%) were reported among the elderly patients. Co-infections in patients with chromoblastomycosis or leprosy are uncommon, but the possibility should always be considered, especially if the patient is undergoing immunosuppressive treatment or is elder.

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Section: Discussionmentioning

confidence: 99%

Chromoblastomycosis-Leprosy Co-Infection in Central West Brazil. Presentation of Three Cases and Literature Review

et al. 2022

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“…This species shows a cosmopolitan distribution and is found in fresh and sea water, including swim-ming pools and aquariums, and generally infects fish, amphibians, and reptiles; rarely, human infection is documented [74]. Disease begins after traumatic contact with animals infected with this bacteria, and immunosuppressed humans are particularly at risk [102].…”

Section: Diversity Of Etiologic Agents Of Cbmmentioning

confidence: 99%

Reviewing the Etiologic Agents, Microbe-Host Relationship, Immune Response, Diagnosis, and Treatment in Chromoblastomycosis

Passero

Cavallone

Belda

2021

Journal of Immunology Research

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Chromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause subcutaneous infections. This disease has been considered an occupational disease, occurring among people working in the field of agriculture, particularly in low-income countries. In 1914, the first case of CBM was described in Brazil, and although efforts have been made, few scientific and technological advances have been made in this area. In the field of fungi and host cell relationship, a very reduced number of antigens were characterized, but available data suggest that ectoantigens bind to the cell membrane of host cells and modulate the phagocytic, immunological, and microbicidal responses of immune cells. Furthermore, antigens cleave extracellular proteins in tissues, allowing fungi to spread. On the contrary, if phagocytic cells are able to present antigens in MHC molecules to T lymphocytes in the presence of costimulation and IL-12, a Th1 immune response will develop and a relative control of the disease will be observed. Despite knowledge of the resistance and susceptibility in CBM, up to now, no effective vaccines have been developed. In the field of chemotherapy, most patients are treated with conventional antifungal drugs, such as itraconazole and terbinafine, but these drugs exhibit limitations, considering that not all patients heal cutaneous lesions. Few advances in treatment have been made so far, but one of the most promising ones is based on the use of immunomodulators, such as imiquimod. Data about a standard treatment are missing in the medical literature; part of it is caused by the existence of a diversity of etiologic agents and clinical forms. The present review summarizes the advances made in the field of CBM related to the diversity of pathogenic species, fungi and host cell relationship, antigens, innate and acquired immunity, clinical forms of CBM, chemotherapy, and diagnosis.

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“…A number of studies have demonstrated that F . monophora exhibits neurotropism or causes primary brain infection without skin damage [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Deletion C-terminal thioesterase abolishes melanin biosynthesis, affects metabolism and reduces the pathogenesis of Fonsecaea monophora

Huang

et al. 2022

PLoS Negl Trop Dis

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Dematiaceous Fonsecaea monophora is one of the major pathogens of chromoblastomycosis. It has been well established that melanization is catalyzed by the type I polyketide synthase (PKS) in F. monophora. Multidomain protein Type I PKS is encoded by six genes, in which the last enzyme thioesterase (TE) catalyzes the cyclization and releases polyketide. Two PKS genes AYO21_03016 (pks1) and AYO21_10638 have been found in F. monophora and both PKS loci have the same gene arrangement but the TE domain in AYO21_10638 is truncated at 3’- end. TE may be the key enzyme to maintain the function of pks1. To test this hypothesis, we constructed a 3’-end 500 bp deletion mutant of AYO21_03016 (Δpks1-TE-C500) and its complemented strain. We profiled metabolome of this mutant and analyzed the consequences of impaired metabolism in this mutant by fungal growth in vitro and by pathogenesis in vivo. Compared with wild-type strain, we found that the mutant repressed pks1 expression and other 5 genes expression levels were reduced by more than 50%, perhaps leading to a corresponding melanin loss. The mutant also reduced sporulation and delayed germination, became vulnerable to various environmental stresses and was less resistance to macrophage or neutrophil killings in vitro, and less virulence in mice footpad model. Metabolomic analysis indicated that many metabolites were remarkably affected in Δpks1-TE-C500, in particular, an increased nicotinamide and antioxidant glutathione. In conclusion, we confirmed the crucial role of C-terminal TE in maintaining fully function of pks1 in F. monophora. Deletion of TE negatively impacts on the synthesis of melanin and metabolites that eventually affect growth and virulence of F. monophora. Any potential inhibitor of TE then could be a novel antifungal target for drug development.

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Immune Sensing and Potential Immunotherapeutic Approaches to Control Chromoblastomycosis

Cited by 9 publications

References 125 publications

Chromoblastomycosis-Leprosy Co-Infection in Central West Brazil. Presentation of Three Cases and Literature Review

Chromoblastomycosis-Leprosy Co-Infection in Central West Brazil. Presentation of Three Cases and Literature Review

Reviewing the Etiologic Agents, Microbe-Host Relationship, Immune Response, Diagnosis, and Treatment in Chromoblastomycosis

Deletion C-terminal thioesterase abolishes melanin biosynthesis, affects metabolism and reduces the pathogenesis of Fonsecaea monophora

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