Absence of CD4<sup>+</sup> T Cells Impairs Host Defence of Mice Infected with <i>Fonsecaea pedrosoi</i>

Sousa, Maria da Glória Teixeira de; Ghosn, Eliver; Almeida, Sandro Rogério de

doi:10.1111/j.1365-3083.2006.01846.x

Cited by 33 publications

(32 citation statements)

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“…However, the cytokine responses were costimulated by exogenous administration of TLR agonists (91). Collectively, the above-described data suggest that CD4 ϩ T-helper cells secreting IFN-␥ may be a useful option for inducing protective immunity against black yeast infections (97,116), and these can be provided by adjunct cytokine immunotherapy (175,176). Specific proinflammatory cytokines, such as IFN-␥, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF, are critical components of host defense which promote the upregulation of chemotaxis, phagocytosis, respiratory burst, and/or degranulation of neutrophils, monocytes, and macrophages (177).…”

Section: Recommended Diagnostics and Treatment Approachesmentioning

confidence: 87%

“…Moreover, mice lacking CD4 ϩ cells, but not CD8 ϩ cells, presented decreased delayed-type hypersensitivity. These animals also produced smaller amounts of IFN-␥ than those in wild-type mice, whereas the levels of this cytokine in mice lacking CD8 ϩ cells were not altered (116). On the other hand, Sotto et al demonstrated that skin macrophages accumulate antigens from black yeasts in their cytoplasm, as homogenous or granular material (93).…”

Section: Adaptive Immunitymentioning

confidence: 99%

Section: Adaptive Immunitymentioning

confidence: 99%

“…Two recent studies showed that CD4 ϩ lymphocytes are potential key cells for the control of chromoblastomycosis (97,116). Notably, immunization of mice with living black yeast conidia reduced a large influx of CD4 ϩ cells into draining lymph nodes (116). In addition, the use of mice lacking CD4 ϩ or CD8 ϩ cells in an experimental chromoblastomycosis model revealed that fungal burdens in the livers and spleens of intraperitoneally infected mice were higher in the absence of CD4 ϩ cells but not influenced by CD8 ϩ lymphocytes.…”

Section: Adaptive Immunitymentioning

confidence: 99%

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Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense

et al. 2014

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SUMMARY Among the melanized fungi, the so-called “black yeasts” and their filamentous relatives are particularly significant as agents of severe phaeohyphomycosis, chromoblastomycosis, and mycetoma in humans and animals. The pathogenicity and virulence of these fungi may differ significantly between closely related species. The factors which probably are of significance for pathogenicity include the presence of melanin and carotene, formation of thick cell walls and meristematic growth, presence of yeast-like phases, thermo- and perhaps also osmotolerance, adhesion, hydrophobicity, assimilation of aromatic hydrocarbons, and production of siderophores. Host defense has been shown to rely mainly on the ingestion and elimination of fungal cells by cells of the innate immune system, especially neutrophils and macrophages. However, there is increasing evidence supporting a role of T-cell-mediated immune responses, with increased interleukin-10 (IL-10) and low levels of gamma interferon (IFN-γ) being deleterious during the infection. There are no standardized therapies for treatment. It is therefore important to obtain in vitro susceptibilities of individual patients' fungal isolates in order to provide useful information for selection of appropriate treatment protocols. This article discusses the pathogenesis and host defense factors for these fungi and their severity, chronicity, and subsequent impact on treatment and prevention of diseases in human or animal hosts.

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Section: Recommended Diagnostics and Treatment Approachesmentioning

confidence: 87%

Section: Adaptive Immunitymentioning

confidence: 99%

Section: Adaptive Immunitymentioning

confidence: 99%

Section: Adaptive Immunitymentioning

confidence: 99%

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Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense

et al. 2014

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“…CD4 ϩ lymphocytes have a role in controlling CBM by secreting IFN-␥ in order to increase cellular immunity responses against F. pedrosoi (218,220,232). Upon mouse inoculation with live conidia, increased T-helper-cell entrance into lymph nodes was observed (232).…”

Section: Adaptive Immune Responsementioning

confidence: 99%

Chromoblastomycosis

et al. 2017

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SUMMARY Chromoblastomycosis (CBM), also known as chromomycosis, is one of the most prevalent implantation fungal infections, being the most common of the gamut of mycoses caused by melanized or brown-pigmented fungi. CBM is mainly a tropical or subtropical disease that may affect individuals with certain risk factors around the world. The following characteristics are associated with this disease: (i) traumatic inoculation by implantation from an environmental source, leading to an initial cutaneous lesion at the inoculation site; (ii) chronic and progressive cutaneous and subcutaneous tissular involvement associated with fibrotic and granulomatous reactions associated with microabscesses and often with tissue proliferation; (iii) a nonprotective T helper type 2 (Th2) immune response with ineffective humoral involvement; and (iv) the presence of muriform (sclerotic) cells embedded in the affected tissue. CBM lesions are clinically polymorphic and are commonly misdiagnosed as various other infectious and noninfectious diseases. In its more severe clinical forms, CBM may cause an incapacity for labor due to fibrotic sequelae and also due to a series of clinical complications, and if not recognized at an early stage, this disease can be refractory to antifungal therapy.

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Fonsecaea pedrosoi‐induced Th17‐cell differentiation in mice is fostered by Dectin‐2 and suppressed by Mincle recognition

Wüthrich

Wang

et al. 2015

Eur J Immunol

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Chromoblastomycosis is a chronic skin infection caused by the pigmented saprophytic mould Fonsecaea pedrosoi. Chronicity of infection can be broken by a coordinated innate recognition of the spores by pattern recognition receptors. While Mincle signaling via theKeywords: Chromoblastomycosis r C-type lectin r Fungi r Dectin-2 r Mincle r T-cell differentiation r Th17 cell Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionChromoblastomycosis is a chronic progressive fungal infection of mammalian skin and subcutaneous tissue that is caused by which gradually enlarge and become verrucous nodules and psoriasis like plaques that may extend as satellites along the lymphatics or disseminate through scratching [5]. Chromoblastomycosis treatment is difficult and most therapeutic attempts provide only a modest rate of success [6,7].Little is known about the protective host defense mechanisms against chromoblastomycosis. Innate immunity mediated by neutrophils and macrophages is thought to be principally responsible for host protection [2,3]. However, the chronic nature of infection with F. pedrosoi may be due to an inappropriate innate immune response [8]. F. pedrosoi is recognized by the C-type lectin receptors (CLRs) Dectin-1 and Mincle, yet fails to induce the production of proinflammatory TNF-α by macrophages and DCs. Inflammatory responses to F. pedrosoi and clearance of infection can be reinstated by exogenous TLR costimulation [8]. Imiquimod (TLR7 ligand) and LPS (TLR4 ligand) application augments TNF-α production and accelerates healing in murine models [8] TLR costimulation does not augment Ag-specific T-cell development in F. pedrosoi-infected miceWe have previously shown that F. pedrosoi spores alone failed to induce innate inflammatory responses by macrophages. The failure of innate recognition could be reinstated by TLR costimulation [8]. To explore whether Ag-specific T-cell responses can be augmented by TLR costimulation we injected F. pedrosoi spore-infected mice with LPS as described [8]. Surprisingly, LPS (TLR4 agonist) and Imiquimod (TLR7 agonist) treatment did not increase the activation (CD44), expansion, and differentiation of Ag-specific 1807 cells as indicated by the numbers and frequencies of activated (CD44 + ) and cytokine producing (IFN-γ and IL-17) 1807 cells (Fig. 1A-E). Thus, unlike innate inflammatory responses, the generation of adaptive cell-mediated immune responses could not be augmented by costimulation of the TLR pathway. sought to investigate whether surface expressed CLRs are involved in the innate recognition of the fungal spores. We cocultured live F. pedrosoi spores with CLR transformed B3Z T-cell hybridoma cells expressing an NFAT-lacZ β-galatosidase reporter of ITAM signaling [15]. In response to spore stimulation, lacZ activity was increased in reporter cells expressing Dectin-1 and Dectin-2 and to a lesser extent MCL (Dectin-3, Clecsf8, or Clec4d) and Mincle, but not in cells expressing FcRγ only (Fig....

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Absence of CD4⁺ T Cells Impairs Host Defence of Mice Infected with Fonsecaea pedrosoi

Cited by 33 publications

References 32 publications

Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense

Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense

Chromoblastomycosis

Fonsecaea pedrosoi‐induced Th17‐cell differentiation in mice is fostered by Dectin‐2 and suppressed by Mincle recognition

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Absence of CD4+ T Cells Impairs Host Defence of Mice Infected with Fonsecaea pedrosoi

Cited by 33 publications

References 32 publications

Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense

Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense

Chromoblastomycosis

Fonsecaea pedrosoi‐induced Th17‐cell differentiation in mice is fostered by Dectin‐2 and suppressed by Mincle recognition

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Absence of CD4⁺ T Cells Impairs Host Defence of Mice Infected with Fonsecaea pedrosoi