Chromoblastomycosis

Walter, Paul; Garin, Y. J. F.; Richard-Lenoble, D

doi:10.1007/bf00442390

Cited by 18 publications

(3 citation statements)

References 25 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Macrophages, along with neutrophils and lymphocytes, are regularly observed within the chronic granulomatous lesions of CBM patients, displaying different degrees of maturation and activation, and they also form multinucleated giant cells that harbor fungi ( 29 , 30 ). In addition, F. pedrosoi cells can be detected in intracytoplasmic vacuoles of skin macrophages ( 61 ). Thus, we investigated whether NLRP3 inflammasome activation would play a part in the microbicidal capacity of macrophages infected with F. pedrosoi .…”

Section: Discussionmentioning

confidence: 99%

The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 Inflammasome

et al. 2017

View full text Add to dashboard Cite

Fonsecaea pedrosoi is the main etiologic agent of chromoblastomycosis (CBM), one of the most prevalent subcutaneous mycosis in tropical and subtropical countries. CBM is a poorly characterized chronic infection that commonly starts after transcutaneous inoculation of conidia and saprophytic hyphae of F. pedrosoi. Recently, we have shown that unlike conidia, hyphae and muriform cells (the parasitic morphotype) of F. pedrosoi promotes an intense inflammatory response pattern in vivo, which comprises the production of an inflammasome-derived cytokine, IL-1β. Nonetheless, the mechanisms underlying IL-1β production and maturation upon F. pedrosoi infection and its functional output in the course of CBM remains unknown. We show here that F. pedrosoi hyphae, differently from conidia, induce IL-1β secretion in both bone marrow-derived dendritic cells and macrophages. Using inhibitors and knockout cells, we demonstrated that the mechanisms underlying IL-1β production by hyphae-infected macrophages were dependent on dectin-1, -2, and -3 receptors and the Syk-NF-kB signaling pathway. Furthermore, F. pedrosoi promoted a NLRP3-dependent inflammasome activation, which required potassium efflux, reactive oxygen species production, phagolysosomal acidification, and cathepsin B release as triggers. IL-1β processing and release was mediated primarily by caspase-1 and, to a lesser extent, by caspase-8-dependent cleavage. Finally, we showed using a murine CBM model that F. pedrosoi elicits a NLRP3-regulated IL-1β and interleukin-18 release in vivo, but without NLRP3 inflammasome activation interfering in the course of the experimental infection.

show abstract

Section: Discussionmentioning

confidence: 99%

The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 Inflammasome

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In histological studies, macrophages have also been observed in the skin of patients infected with F. pedrosoi, and after phagocytosis, muriform cells are contained in cytoplasmic vacuoles. Although ultrastructural analysis by scanning electron microscopy suggested minor to moderate changes in the outermost layers of the cell walls of muriform cells, only a small number of yeasts showed signs of irreversible degeneration [129]. Furthermore, in vitro experiments showed that activated macrophages from Swiss mice inhibit or delay the transformation of conidia of F. pedrosoi into hyphae, although these macrophages were unable to kill intracellular fungi even in the presence of an oxidative response [105].…”

Section: Immune Response In 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

View full text Add to dashboard Cite

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.

show abstract

“…Intracellular muriform cells are resistant to the microbicidal action of APCs [9,10], possibly due to the scavenger action of fungal melanin, which inhibits the microbicidal action of macrophages, as well as other phagocytic cells. Consequently, the fungus persists in the vertebrate host, potentializing the inflammatory response and triggering an adaptive immune response.…”

Section: Introductionmentioning

confidence: 99%

New Immunological Markers in Chromoblastomycosis—The Importance of PD-1 and PD-L1 Molecules in Human Infection

Cavallone,

Belda,

de Carvalho

et al. 2023

JoF

View full text Add to dashboard Cite

The pathogenesis of chromoblastomycosis (CBM) is associated with Th2 and/or T regulatory immune responses, while resistance is associated with a Th1 response. However, even in the presence of IFN-γ, fungi persist in the lesions, and the reason for this persistence is unknown. To clarify the factors associated with pathogenesis, this study aimed to determine the polarization of the cellular immune response and the densities of cells that express markers of exhaustion in the skin of CBM patients. In the skin of patients with CBM, a moderate inflammatory infiltrate was observed, characterized primarily by the occurrence of histiocytes. Analysis of fungal density allowed us to divide patients into groups that exhibited low and high fungal densities; however, the intensity of the inflammatory response was not related to mycotic loads. Furthermore, patients with CBM exhibited a significant increase in the number of CD4+ and CD8+ cells associated with a high density of IL-10-, IL-17-, and IFN-γ-producing cells, indicating the presence of a chronic and mixed cellular immune response, which was also independent of fungal load. A significant increase in the number of PD-1+ and PD-L1+ cells was observed, which may be associated with the maintenance of the fungus in the skin and the progression of the disease.

show abstract

Chromoblastomycosis

Cited by 18 publications

References 25 publications

The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 Inflammasome

The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 Inflammasome

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

New Immunological Markers in Chromoblastomycosis—The Importance of PD-1 and PD-L1 Molecules in Human Infection

Contact Info

Product

Resources

About