Cellular and molecular mechanisms of resistance to oral Candida albicans infections

Saunus, Jodi M.; Kazoullis, Andrea; Farah, Camile S.

doi:10.2741/3085

Cited by 36 publications

(29 citation statements)

References 108 publications

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“…1 Oral candidiasis is an important health problem that disproportionately affects HIV-infected and AIDS patients, with 90% of AIDS patients being afflicted with oral candidiasis. 2 Unfortunately, candidiasis has limited treatment options, many of which are refractory to traditional treatments. 3 Since the initiation of highly active antiretroviral therapy (HAART) there has been a decrease in the incidence of oropharyngeal candidiasis.…”

Section: Introductionmentioning

confidence: 99%

Colonization byCandidaSpecies of the Oral and Vaginal Mucosa in HIV-Infected and Noninfected Women

Merenstein

Wang

et al. 2013

AIDS Research and Human Retroviruses

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Candidiasis in HIV/AIDS patients continues to be a public health problem. Effective antifungal therapies are few in number and have inherent problems such as selecting for drug-resistant strains of Candida species. To evaluate the state of Candida colonization of the oral and vaginal mucosa, we recruited 80 women, both HIVinfected and HIV-uninfected, from the Women's Interagency HIV Study (WIHS). Diet diaries were collected by participants to examine the role of diet on fungal growth. Baseline studies were initially done in participants that followed the colonization of both mucosal sites over 0-90 days. The most common Candida species from both groups of patients were C. albicans and C. glabrata. Among the HIV-infected cohort, the percentage of participants who were positive for Candida spp. was higher than in the HIV-uninfected control group. Furthermore, the frequency of colonization (1 episode versus > 1 episode) was also increased in the HIV-infected cohort. These data indicate that Candida species remain an important component of the microbial community in both populations.

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Section: Introductionmentioning

confidence: 99%

Colonization byCandidaSpecies of the Oral and Vaginal Mucosa in HIV-Infected and Noninfected Women

Merenstein

Wang

et al. 2013

AIDS Research and Human Retroviruses

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“…Moreover, the mechanisms by which IL-17 exerts its effects in the context of candidiasis are not fully understood. IL-17 is essential to control the neutrophil and antimicrobial peptide responses to candidiasis (31,(34)(35)(36). In addition, a recent study suggests that IL-17 may also be important for driving NK cell function in disseminated disease through a mechanism dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF) (37).…”

Section: Discussionmentioning

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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“…In addition to IL-17 discussed above, these include factors that promote development and recruitment of neutrophils, such as GM-CSF, G-CSF, CXCL1 and CXCL2 [130, 144]. Similarly, cytokines that promote phagocyte killing and recruitment, such as TNFα, IL-6, IL-1β and IFNγ, are key in host defense against C. albicans .…”

Section: Antifungal Mechanisms: Soluble Factorsmentioning

confidence: 99%

Beyond Candida albicans: Mechanisms of immunity to non-albicans Candida species

Whibley

Gaffen

2015

Cytokine

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The fungal genus Candida encompasses numerous species that inhabit a variety of hosts, either as commensal microbes and/or pathogens. Candida species are a major cause of fungal infections, yet to date there are no vaccines against Candida or indeed any other fungal pathogen. Our knowledge of immunity to Candida mainly comes from studies on C. albicans, the most frequent species associated with disease. However, non-albicans Candida (NAC) species also cause disease and their prevalence is increasing. Although research into immunity to NAC species is still at an early stage, it is becoming apparent that immunity to C. albicans differs in important ways from non-albicans species, with important implications for treatment, therapy and predicted demographic susceptibility. This review will discuss the current understanding of immunity to NAC species in the context of immunity to C. albicans, and highlight as-yet unanswered questions.

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Cellular and molecular mechanisms of resistance to oral Candida albicans infections

Cited by 36 publications

References 108 publications

Colonization byCandidaSpecies of the Oral and Vaginal Mucosa in HIV-Infected and Noninfected Women

Colonization byCandidaSpecies of the Oral and Vaginal Mucosa in HIV-Infected and Noninfected Women

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

Beyond Candida albicans: Mechanisms of immunity to non-albicans Candida species

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