Role of IFN-gamma in immune responses to Candida albicans infections

Gozalbo, Daniel

doi:10.2741/4281

Cited by 49 publications

(39 citation statements)

References 106 publications

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“…A–C). We measured the pro‐inflammatory cytokines IL‐6, IL‐1β and TNF‐α, expressed by antigen presenting cells in response to fungal antigens (Qin et al ., ; van de Veerdonk et al ., ), as well as the Th response cytokines IFN‐γ (Th1) and IL‐17 (Th17), both known to allow resistance towards colonization of fungi such as Aspergillus fumigatus (van de Veerdonk et al ., ) and Candida albicans (Gaffen et al ., ; Gozalbo et al ., ) and the Th2 cytokine IL‐13, involved in allergic response (Gagliani and Huber, ). We also measured the level of IL‐10, an anti‐inflammatory cytokine involved in immune tolerance towards fungi (Roussey et al ., ).…”

Section: Resultsmentioning

confidence: 99%

Population genomics reveals evolution and variation ofSaccharomyces cerevisiaein the human and insects gut

Ramazzotti

Stefanini

Paola

et al. 2018

Environmental Microbiology

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Summary The quest to discover the variety of ecological niches inhabited by Saccharomyces cerevisiae has led to research in areas as diverse as wineries, oak trees and insect guts. The discovery of fungal communities in the human gastrointestinal tract suggested the host's gut as a potential reservoir for yeast adaptation. Here, we report the existence of yeast populations associated with the human gut (HG) that differ from those isolated from other human body sites. Phylogenetic analysis on 12 microsatellite loci and 1715 combined CDSs from whole‐genome sequencing revealed three subclusters of HG strains with further evidence of clonal colonization within the host's gut. The presence of such subclusters was supported by other genomic features, such as copy number variation, absence/introgressions of CDSs and relative polymorphism frequency. Functional analysis of CDSs specific of the different subclusters suggested possible alterations in cell wall composition and sporulation features. The phenotypic analysis combined with immunological profiling of these strains further showed that sporulation was related with strain‐specific genomic characteristics in the immune recognition pattern. We conclude that both genetic and environmental factors involved in cell wall remodelling and sporulation are the main drivers of adaptation in S. cerevisiae populations in the human gut.

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Section: Resultsmentioning

confidence: 99%

Population genomics reveals evolution and variation ofSaccharomyces cerevisiaein the human and insects gut

Ramazzotti

Stefanini

Paola

et al. 2018

Environmental Microbiology

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“…[262829] In addition, serum interferon-gamma (IFN-γ) levels are markedly elevated in patients with fungal infections,[3031] IFN-γ is a critical factor for defense against fungal infections. [313233] In vitro , PCT secretion has been found to be inhibited by IFN-γ. [34] Thus, PCT concentrations in fungal sepsis might be regulated by IFN-γ levels.…”

Section: Discussionmentioning

confidence: 99%

Serum procalcitonin levels distinguish Gram-negative bacterial sepsis from Gram-positive bacterial and fungal sepsis

Rong

Guo

et al. 2016

J Res Med Sci

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Background:Serum procalcitonin (PCT) levels differ in patients with bacterial or fungal infections and are significantly elevated in patients with Gram-negative bacteremia. We evaluated the diagnostic accuracy of different inflammatory markers to discriminate sepsis caused by different pathogens.Materials and Methods:We included 328 episodes of bacteremia from 292 patients with sepsis and 31 patients with suspected sepsis in this study. Medical records of patients who had bacteremia caused by Gram-negative bacteria (Gram-negative), Gram-positive bacteria (Gram-positive) or fungi were reviewed, and information about PCT and other inflammatory markers was recorded. The diagnostic performance of inflammatory markers was calculated via receiver operating characteristic (ROC) curves.Results:Serum PCT levels in Gram-negative, Gram-positive, and fungal sepsis were 7.47 (interquartile range [IQR]: 1.09–41.26) ng/mL, 0.48 (IQR: 0.15–2.16) ng/mL, and 0.60 (IQR: 0.14–2.06) ng/mL, respectively (P < 0.001). ROC analysis revealed an optimal cut-off value of 2.44 ng/mL for PCT in discriminating Gram-negative sepsis from Gram-positive sepsis, which yielded a sensitivity of 68.4% and a specificity of 77.1%. An optimal cut-off value of 3.11 ng/mL for PCT in discriminating Gram-negative sepsis from fungal sepsis, led to a sensitivity of 63.9% and specificity of 93.3%. Neither PCT nor other inflammatory markers could be used to distinguish between Gram-positive and fungal sepsis.Conclusion:Serum PCT levels were significantly higher in patients with Gram-negative sepsis than in those with Gram-positive or fungal sepsis. PCT is a potential sensitive biomarker for distinguishing Gram-negative sepsis from Gram-positive and fungal sepsis.

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“…Although we emphasized the role of IL‐10 in the iNKT cell‐derived host responses to C. albicans infection, we have to consider the fact that the levels of IFN‐γ and IL‐12 were higher in Jα18 −/− mice after C. albicans infection. IFN‐γ, a major determinant of Th1 maturation, promotes candidacidal activity of phagocytes by enhancing their phagocytosis and intracellular killing of C. albicans . IL‐12 is a cytokine produced predominantly by innate immune cells and plays a critical role in inducing Th1 responses.…”

Section: Discussionmentioning

confidence: 99%

Activation of murine invariant NKT cells promotes susceptibility to candidiasis by IL‐10 induced modulation of phagocyte antifungal activity

et al. 2016

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Invariant NKT (iNKT) cells play an important role in a variety of antimicrobial immune responses due to their ability to produce high levels of immune-modulating cytokines.Here, we investigated the role of iNKT cells in host defense against candidiasis using Jα18-deficient mice (Jα18 −/− ), which lack iNKT cells. Jα18 −/− mice were more resistant to the development of lethal candidiasis than wild-type (WT) mice. In contrast, treatment of WT mice with the iNKT cell activating ligand α-galactosylceramide markedly enhanced their mortality after infection with Candida albicans. Serum IL-10 levels were significantly elevated in WT mice in response to infection with C. albicans. Futhermore, IL-10 production increased after in vitro coculture of peritoneal macrophages with iNKT cells and C. albicans. The numbers of peritoneal macrophages, the production of IL-1β and IL-18, and caspase-1 activity were also significantly elevated in Jα18 −/− mice after infection with C. albicans. The adoptive transfer of iNKT cells or exogenous administration of IL-10 into Jα18 −/− reversed susceptibility to candidiasis to the level of WT mice. These results suggest that activation of iNKT cells increases the initial severity of C. albicans infection, most likely mediated by IL-10 induced modulation of macrophage antifungal activity.Keywords: Candidiasis r IL-10 r Inflammasome r iNKT cells r Macrophages Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionCandida species, and most commonly Candida albicans, are opportunistic fungal pathogens that cause most of the widespread nosocomial bloodstream infections worldwide [1,2]. Candida albicans is part of the normal microbial flora in human beings and domesCorrespondence: Dr. Yukio Ishii e-mail: ishii-y@md.tsukuba.ac.jp tic animals. However, under conditions of immune dysfunction, C. albicans switches from a commensal to a pathogenic organism capable of infecting a variety of tissues and can subsequently cause fatal systemic diseases [3,4].Several host factors, including both the innate and adaptive immune systems, are required for the control of C. albicans infection [5][6][7] defense against systemic C. albicans infection while T cells are critical for controlling mucocutaneous C. albicans infection [7][8][9]. With regard to T-cell immunity, resistance to C. albicans was long considered to be mediated by Th1 immunity because Th1 cytokines, including IFN-γ and TNF-α, activate macrophages and neutrophils to enter a candidacidal state, and Th2 cytokines, such as IL-4 and IL-13, inhibit Th1 development and deactivate phagocytic effector cells [10,11]. Several recent studies have revealed that Th17 cells plays an essential role in immunity to C. albicans, especially immunity to mucocutaneous candidiasis, via the production of IL-17 that acts on epithelial and mesenchymal cells to induce neutrophil-attracting chemokines [9,12,13]. Natural killer T (NKT) cells are an unconventional type of T cell that expresses both TCRs and...

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Role of IFN-gamma in immune responses to Candida albicans infections

Cited by 49 publications

References 106 publications

Population genomics reveals evolution and variation ofSaccharomyces cerevisiaein the human and insects gut

Population genomics reveals evolution and variation ofSaccharomyces cerevisiaein the human and insects gut

Serum procalcitonin levels distinguish Gram-negative bacterial sepsis from Gram-positive bacterial and fungal sepsis

Activation of murine invariant NKT cells promotes susceptibility to candidiasis by IL‐10 induced modulation of phagocyte antifungal activity

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