Human inborn errors of immunity underlying superficial or invasive candidiasis

Puel, Anne

doi:10.1007/s00439-020-02141-7

Cited by 67 publications

(75 citation statements)

References 138 publications

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“…Cytokine analysis of culture medium of both isolated skin cells stimulated with HK S. aureus and human skin explants infected ex vivo with S. aureus showed the production of cytokines involved in skin inflammation and tissue repair. Genetic evidence has highlighted a key role for IL-17-mediated immunity in protection against S. aureus skin infection, but not invasive staphylococcal disease, similarly to what has been observed for C. albicans infections (36,37). IL-17 enhances the recruitment of neutrophils, which can kill S. aureus, to the site of infection, and stimulates the production of antimicrobial peptides (AMPs) that can be directly bactericidal (38)(39)(40).…”

Section: Discussionmentioning

confidence: 75%

“…Interestingly, this could be achieved through alpha-toxin that has been shown to modulate mouse CD4 + T cell differentiation limiting Th1 while promoting Th17 responses ( 57 ). However, once the skin is breached, the local immunity is dampened or the bacterial load is exceedingly high, this local response is no longer sufficient to control S. aureus ( 37 ). Indeed, the importance of antibodies and Th1 cells in controlling systemic S. aureus infections has been highlighted ( 25 , 58 ).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, this seems to be a common characteristic of barrier-protective Trm cells. In addition, since some inborn errors of IL-17 immunity predispose not only to skin but also to lung S. aureus infection ( 37 ), the presence of S. aureus -specific CD4 + Tsrm cells in the lungs and their phenotype should be assessed.…”

Section: Discussionmentioning

confidence: 99%

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Staphylococcus aureus-Specific Tissue-Resident Memory CD4+ T Cells Are Abundant in Healthy Human Skin

Hendriks

Mnich

Clemente³

et al. 2021

Front. Immunol.

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The skin is an immunocompetent tissue that harbors several kinds of immune cells and a plethora of commensal microbes constituting the skin microbiome. Staphylococcus aureus is a prominent skin pathogen that colonizes a large proportion of the human population. We currently have an incomplete understanding of the correlates of protection against S. aureus infection, however genetic and experimental evidence has shown that CD4+ T cells play a key role in orchestrating a protective anti-S. aureus immune response. A high S. aureus-specific memory CD4+ T cell response has been reported in the blood of healthy subjects. Since T cells are more abundant in the skin than in blood, we hypothesized that S. aureus-specific CD4+ T cells could be present in the skin of healthy individuals. Indeed, we observed proliferation of tissue-resident memory CD4+ T cells and production of IL-17A, IL-22, IFN-γ and TNF-β by cells isolated from abdominal skin explants in response to heat-killed S. aureus. Remarkably, these cytokines were produced also during an ex vivo epicutaneous S. aureus infection of human skin explants. These findings highlight the importance of tissue-resident memory CD4+ T cells present at barrier sites such as the skin, a primary entry site for S. aureus. Further phenotypical and functional characterization of these cells will ultimately aid in the development of novel vaccine strategies against this elusive pathogen.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

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Staphylococcus aureus-Specific Tissue-Resident Memory CD4+ T Cells Are Abundant in Healthy Human Skin

Hendriks

Mnich

Clemente³

et al. 2021

Front. Immunol.

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“… 2015 ; Li et al . 2017 ; Puel 2020 ). Consistently, mice with defects in the IL-17 signalling pathway display a reduced ability to cope with C. albicans administered via oropharyngeal or epicutaneous routes (Conti et al .…”

Section: The Hostmentioning

confidence: 99%

The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives

d’Enfert

Kaune

Alaban

et al. 2020

FEMS Microbiology Reviews

187

134

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Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients.

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“…However, some STAT1 partial loss of function (LOF) patients suffer from chronic colitis, as well as severe infections [7, 8]. On the other hand, individuals with STAT1 gain-of-function (GOF) mutations suffer most frequently from mucocutaneous diseases, in part due to depressed levels of T H 17 cells, thereby attributing important regulatory functions to STAT1 [9, 10].…”

Section: Introductionmentioning

confidence: 99%

Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome

Marié

Brambilla

Azzouz

et al. 2021

Preprint

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Maintenance of immune homeostasis involves a synergistic relationship between the host and the microbiome. Canonical interferon (IFN) signaling controls responses to acute microbial infection, through engagement of the STAT1 transcription factor. However, the contribution of tonic levels of IFN to immune homeostasis in absence of acute infection remains largely unexplored. We report that STAT1 KO mice spontaneously developed an inflammatory disease marked by myeloid hyperplasia and splenic accumulation of hematopoietic stem cells. Moreover, these animals developed inflammatory bowel disease. Profiling gut bacteria revealed a profound dysbiosis in absence of tonic IFN signaling, which triggered expansion of TH17 cells and loss of splenic Treg cells. Resolution of dysbiosis by antibiotic treatment averted the TH17 bias, and blocking IL17 signaling prevented myeloid expansion and splenic stem cell accumulation. Thus, tonic IFNs regulate gut microbial ecology, which is crucial for maintaining physiologic immune homeostasis and preventing inflammation.

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Human inborn errors of immunity underlying superficial or invasive candidiasis

Cited by 67 publications

References 138 publications

Staphylococcus aureus-Specific Tissue-Resident Memory CD4+ T Cells Are Abundant in Healthy Human Skin

Staphylococcus aureus-Specific Tissue-Resident Memory CD4+ T Cells Are Abundant in Healthy Human Skin

The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives

Tonic interferon restricts pathogenic IL-17-driven inflammatory disease via balancing the microbiome

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