Sensing of mammalian IL-17A regulates fungal adaptation and virulence

Zelante, Teresa; Iannitti, Rossana Giulietta; Luca, Antonella De; Arroyo, Javier; Blánco, N.; Servillo, Giuseppe; Sanglard, Dominique; Reichard, Utz; Palmer, Glen E.; Latgé, Jean‐Paul; Puccetti, Paolo; Romani, Luigina

doi:10.1038/ncomms1685

Cited by 86 publications

(71 citation statements)

References 43 publications

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“…Employing murine knockout intragastric infection model, followed by in vivo IL-17A monoclonal antibody inhibition, Iannitti's group confirmed that absence of functional IL-17A pathways increased resistance to C. albicans, while also observing that IL-17A could increase fungal adhesion and prevent phagocytosis and fungal killing. Iannitti's group detected a similar response in a similar Aspergillus fumigatus model [4,5].…”

Section: Fungal Strategiesmentioning

confidence: 76%

“…IL-22, already accepted as a cytokine involved in the co-ordination of responses to a variety of pathogens, is often coexpressed with IL-17A that enables balance between proinflammatory and tissue protective responses. Iannitti discussed the importance of IL-17 in the establishment of Candida infection: this cytokine could be protective or pathogenic in antifungal responses as it binds both fungal and host cells [4,5].…”

Section: Fungal Strategiesmentioning

confidence: 99%

“…After establishing that IL-17A may bind Candida albicans via fluorescence microscopy, Iannitti's group explored host-C. albicans interactions with a view to determining the relative benefits of IL-17A activity in vivo [4,5]. Employing murine knockout intragastric infection model, followed by in vivo IL-17A monoclonal antibody inhibition, Iannitti's group confirmed that absence of functional IL-17A pathways increased resistance to C. albicans, while also observing that IL-17A could increase fungal adhesion and prevent phagocytosis and fungal killing.…”

Section: Fungal Strategiesmentioning

confidence: 99%

“…TOR pathways were, however, downregulated as a general picture of an induced starvation state. Iannitti's group concluded that fungal cells could actively sense host cytokine responses and respond accordingly as a strategy for evading such responses [4,5]. Further work will involve continuing exploration of time-and dose-dependent responses of C. albicans to IL-17A and the reciprocal relationship with host immune responses, a theme that may help drive novel drug development for immunosuppressed patients colonized with antifungal resistant C. albicans strains.…”

Section: Fungal Strategiesmentioning

confidence: 99%

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Conference Scene: Understanding Pathogen Evasion of Host Immunity

Ward

2012

Immunotherapy

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This novel conference organized by EuroSciCon hosted scientists from across Europe with research interests varying in pathogen type and branch of immunology. The conference was intentionally convened to promote cross-disciplinary discussion and interaction among immunologists differing in research background. The day involved several talks in addition to a question and answer session chaired by an expert panel, allowing researchers to discuss and integrate their diverse interests and findings in a novel forum. This report highlights topical research in bacterial, viral, fungal and parasitic interactions with host immunity.

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Section: Fungal Strategiesmentioning

confidence: 76%

Section: Fungal Strategiesmentioning

confidence: 99%

Section: Fungal Strategiesmentioning

confidence: 99%

Section: Fungal Strategiesmentioning

confidence: 99%

See 2 more Smart Citations

Conference Scene: Understanding Pathogen Evasion of Host Immunity

Ward

2012

Immunotherapy

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“…Experimental vaccines for Candida and other pathogenic fungi have been shown to require intact Th17 responses (16,17). In contrast, it has been suggested that IL-17A may act directly on C. albicans to increase its virulence in a gastric model of candidiasis (18). Therefore, understanding the correlates of immunity and particularly the impact of IL-17 activity in the context of Candida infections is important in designing new drugs or preventive strategies to treat candidiasis.…”

mentioning

confidence: 99%

A Candida albicans Strain Expressing Mammalian Interleukin-17A Results in Early Control of Fungal Growth during Disseminated Infection

et al. 2015

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dCandida albicans is normally a commensal fungus of the human mucosae and skin, but it causes life-threatening systemic infections in hospital settings in the face of predisposing conditions, such as indwelling catheters, abdominal surgery, or antibiotic use. Immunity to C. albicans involves various immune parameters, but the cytokine interleukin-17A (IL-17A) (also known as IL-17) has emerged as a centrally important mediator of immune defense against both mucosal and systemic candidiasis. Conversely, IL-17A has been suggested to enhance the virulence of C. albicans, indicating that it may exert detrimental effects on pathogenesis. In this study, we hypothesized that a C. albicans strain expressing IL-17A would exhibit reduced virulence in vivo.To that end, we created a Candida-optimized expression cassette encoding murine IL-17A, which was transformed into the DAY286 strain of C. albicans. Candida-derived IL-17A was indistinguishable from murine IL-17A in terms of biological activity and detection in standard enzyme-linked immunosorbent assays (ELISAs). Expression of IL-17A did not negatively impact the growth of these strains in vitro. Moreover, the IL-17A-expressing C. albicans strains showed significantly reduced pathogenicity in a systemic model of Candida infection, mainly evident during the early stages of disease. Collectively, these findings suggest that IL-17A mitigates the virulence of C. albicans. Candida albicans is a commensal fungus of human skin and mucosal surfaces. Although normally nonpathogenic, C. albicans can cause disease in settings of immunodeficiency, abdominal surgery or otherwise disrupted barriers, antibiotic use, or other conditions (1, 2). By far the most serious form of candidiasis is a systemic infection characterized by fungal invasion into target organs, particularly the liver, kidney, and brain (3). Disseminated candidiasis is the 4th most common cause of hospital-acquired infections and has a high mortality rate (averaging 40%) (4).In recent years, accumulating data have implicated the cytokine interleukin-17A (IL-17A) (also known as IL-17) in immunity to Candida and other fungi (5, 6). IL-17A-and IL-17 receptordeficient mice are highly susceptible to candidemia (7-9). Similarly, humans with defects in the IL-17 pathway are especially sensitive to Candida infections; the defects arise from mutations in genes controlling IL-17 signaling (ACT1, IL17RA, IL17RC, and IL17F) or genes that drive Th17 cell differentiation (DECTIN1, CARD9, STAT3, STAT1, IL12B, and IL12RB) or arise in individuals with naturally occurring anti-IL-17 antibodies (occurring in certain thymomas and AIRE deficiency, also known as autoimmune polyglandular syndrome type 1 [APS-1] or autoimmune polyendocrinopathy candidiasis ectodermal dystrophy [APECED]) (10, 11).Although Candida infections can be treated pharmacologically, currently available antifungal medications are limited by significant drug-drug interactions, the emergence of drug resistance, and toxicity (12, 13). To date, there are no vaccines availab...

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Microbiota control of a tryptophan–AhR pathway in disease tolerance to fungi

et al. 2014

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An increased understanding of the importance of microbiota in shaping the host's immune and metabolic activities has rendered fungal interactions with their hosts more complex than previously appreciated. The aryl hydrocarbon receptor (AhR) has a pivotal role in connecting tryptophan catabolism by microbial communities and the host's own pathway of tryptophan metabolite production with the orchestration of T-cell function. AhR activation by a Lactobacillus-derived AhR ligand leads to the production of IL-22 to the benefit of mucosal defense mechanisms, an activity upregulated in the absence of the host tryptophan catabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO1), which is required for protection from fungal diseases ("disease tolerance"). As AhR activation in turn leads to the activation-in a feedback fashion-of IDO1, the regulatory loop involving AhR and IDO1 may have driven the coevolution of commensal fungi with the mammalian immune system and the microbiota, to the benefit of host survival and fungal commensalism. This review will discuss the essential help the microbiota provides in controlling the balance between the dual nature of the fungal-host relationship, namely, commensalism vs. infection. Keywords:Aryl hydrocarbon receptor r Indoleamine 2,3-dioxygenase 1 r IL-22 r Microbiota r Mycobiome r Tryptophan IntroductionThe role of commensal fungi (referred to as the mycobiome, reviewed in [1][2][3] in educating the immune system in health and disease has been increasingly appreciated (reviewed in [4]). Such a long-established commensalism indicates that commensal fungi are an integral part of the eukaryotic host. To date, the human fungal community has been shown to be comprised of Candida and Malassezia on mucosal surfaces, skin, and oral cavity, Pneumocystis jirovecii, a lung commensal, and consensus members of the basal human salivary mycobiome includCorrespondence: Prof. Luigina Romani e-mail: luigina.romani@unipg.it ing Candida/Pichia, Cladosporium/Davidiella, Alternaria/Lewia, Aspergillus/Emericella/Eurotium, Fusarium/Gibberella, Cryptococcus/Filobasidiella, and Aureobasidium [1,[5][6][7]. Given that different body sites harbor specific fungal populations, unique mycobiome patterns are associated with various diseases. By interfacing with the microbiome, as well as with its host, the mycobiome plays an important role in health and disease, most likely by regulating immune reactivity at mucosal surfaces where an integration of physical and metabolic factors is of fundamental importance (reviewed in [1,8,9]). Indeed, owing to their capacity to activate immune responses, commensal fungi have been shown to influence immune reactions at local [10][11][12] and distal sites [13,14], such as in colitis and allergy in the airways. Conversely, owing to microbial dysbiosis or defects in the innate or adaptive immune systems, commensal fungi may shift from commensalism to parasitism, and they may cause severe fungal infections andwww.eji-journal.eu Eur. J. Immunol. 2014. 44: 3192-3200 HIGHLIGHTS 3193dise...

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Sensing of mammalian IL-17A regulates fungal adaptation and virulence

Cited by 86 publications

References 43 publications

Conference Scene: Understanding Pathogen Evasion of Host Immunity

Conference Scene: Understanding Pathogen Evasion of Host Immunity

A Candida albicans Strain Expressing Mammalian Interleukin-17A Results in Early Control of Fungal Growth during Disseminated Infection

Microbiota control of a tryptophan–AhR pathway in disease tolerance to fungi

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