Candida innate immunity at the mucosa

Richardson, Jonathan P.; Moyes, David L.; Ho, Jemima; Naglik, Julian R.

doi:10.1016/j.semcdb.2018.02.026

Cited by 59 publications

(50 citation statements)

References 177 publications

(201 reference statements)

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“…Our knowledge about the immune response upon invasion of pathogens has advanced considerably during recent decades. In this regard, for more insights, comprehensive reviews have been published in the literature on this subject [55,56]. Briefly, once C. albicans impairs the first line defense, represented by epithelial cells, antimicrobial peptides and signaling molecules are released, thus leading to innate immune cell recruitment.…”

Section: Immunology: Rvvc As An Immunodeficiencymentioning

confidence: 99%

Recurrent Vulvovaginal Candidiasis: An Immunological Perspective

et al. 2020

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Vulvovaginal candidiasis (VVC) is a widespread vaginal infection primarily caused by Candida albicans. VVC affects up to 75% of women of childbearing age once in their life, and up to 9% of women in different populations experience more than three episodes per year, which is defined as recurrent vulvovaginal candidiasis (RVVC). RVVC results in diminished quality of life as well as increased associated healthcare costs. For a long time, VVC has been considered the outcome of inadequate host defenses against Candida colonization, as in the case of primary immunodeficiencies associated with persistent fungal infections and insufficient clearance. Intensive research in recent decades has led to a new hypothesis that points toward a local mucosal overreaction of the immune system rather than a defective host response to Candida colonization. This review provides an overview of the current understanding of the host immune response in VVC pathogenesis and suggests that a tightly regulated fungus–host–microbiota interplay might exert a protective role against recurrent Candida infections.

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Section: Immunology: Rvvc As An Immunodeficiencymentioning

confidence: 99%

Recurrent Vulvovaginal Candidiasis: An Immunological Perspective

et al. 2020

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“…Innate immunity contributes to fungal clearance during mucosal C. albicans infection [23]. Consequently, we determined the impact of TRAF1 on fungal clearance at the early stage of C. albicans infection.…”

Section: Traf1-regulated Immune Response Controls Fungal Burdenmentioning

confidence: 99%

TRAF1 suppresses antifungal immunity through CXCL1-mediated neutrophil recruitment during Candida albicans intradermal infection

et al. 2020

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Background: Candida albicans is the most common opportunistic human fungal pathogen. The chemokine ligand CXCL1 plays a protective role in fungal infection through the recruitment of neutrophils. TRAF1 (tumor necrosis factor-associated factor 1) can be highly induced by proinflammatory stimuli such as LPS and TNF and has been implicated in septic shock. However, the role of TRAF1 in infection, especially fungal infection, remains elusive. Herein, we reveal that TRAF1 suppresses the antifungal immune response to Candida albicans intradermal infection through the regulation of CXCL1 induction and neutrophil recruitment. Methods: A mouse model of C. albicans intradermal infection was established. The Traf1 −/− mice and Traf1 −/− immortalized human keratinocytes were generated. The p65 inhibitor triptolide, STAT1 inhibitor fludarabine, neutrophil-depletion antibody Ly6G, and neutralizing antibody for CXCL1 were utilized. The expression of proinflammatory cytokines and chemokines was assessed by real-time PCR and ELISA, and the activation of signaling molecules was analyzed by Western blotting. Hematoxylin and eosin staining and periodic acid Schiff staining were used for histology or fungal detection, respectively. The immunofluorescence and flow cytometry analyses were employed in the assessment of immune cell infiltration. Bone marrow transplantation and adoptive transfer experiments were conducted to establish a role for TRAF1 in the macrophage compartment in fungal skin infection. Results: TRAF1-deficient mice demonstrated improved control of Candida albicans intradermal infection, and concomitant increase in neutrophil recruitment and reduction in fungal burden. The chemokine CXCL1 was upregulated in the TRAF1-deficient macrophages treated with heat-killed C. albicans. Mechanistically, TRAF1deficient macrophages showed increased activation of transcription factor NFκB p65. The human CXCL8 was also highly induced in the TRAF1-deficient human keratinocytes upon TNF stimulation through decreasing the activation of transcription factor STAT1. TRAF1-deficient macrophages played a critical role in containing the C. albicans skin infection in vivo. Conclusion: TRAF1-deficient mice can better control fungal infection in the skin, a process attributable to the CXCL-neutrophil axis. Mechanistically, TRAF1 likely regulates CXCL1 expression in both macrophages and keratinocytes through the transcriptional factor NFκB and STAT1, respectively. Our finding offers new insight into the understanding of the immune regulatory mechanisms in host defense against C. albicans infection.

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“…These molecules will eventually help to clear fungal invasion and recruit more immune cells to the infection foci, such as neutrophils, macrophages and innate Th17 cells. (Verma et al, 2017a;Richardson et al, 2019). Therefore, we will give a brief general overview of the current view of anti-Candida immunity at the mucosae (Figure 1).…”

Section: Anti-candida Innate Immunity At the Mucosamentioning

confidence: 99%