Role of Adaptive Immunity in the Pathogenesis of<i>Candida albicans</i>Keratitis

Chen, Hao; Niu, Jingyi; Xie, Liping

doi:10.1167/iovs.08-3104

Cited by 29 publications

(24 citation statements)

References 23 publications

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“…Local production of antibodies specific to different viral or microbial agents in cornea has been documented [14][15][16]. In our study some corneas were positive for immunoglobulins and inflammatory cells simultaneously.…”

Section: Discussionsupporting

confidence: 61%

Pathological findings in cornea tissue of patients with penetrating keratoplasty.

Kostelná

Rosocha²,

Paulíková³

et al. 2010

Folia Histochem Cytobiol.

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Abstract:The aim of this clinical study was to examine corneas extracted from the patients during penetrating keratoplasty for the presence of immunoglobulins and inflammatory cells that can be warning for the graft failure. Individual clinical diagnoses were correlated to the presence of the inflammatory signs in corneal tissue. The signs of inflammation in corneal layers were detected especially in group of patients classified as viral keratitis but were also found in corneas of patients with degenerative diseases of the cornea. Depending on the number of keratoplasties no statistical difference in analysed parameters was found. Inflammatory process represented by slight positive presence cellular infiltration and/or immunoglobulins could be present in corneal tissue also in absence of acute manifestation. Histological and immunohistochemical evaluation of corneal tissue from patients undergoing penetrating keratoplasty could improve estimation of correct diagnosis. Subsequently prompt adequate therapy could improve worse prognosis of corneal graft with evident immune process.

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Section: Discussionsupporting

confidence: 61%

Pathological findings in cornea tissue of patients with penetrating keratoplasty.

Kostelná

Rosocha²,

Paulíková³

et al. 2010

Folia Histochem Cytobiol.

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“…All animals were maintained in pathogen-free facility and were 6-10 weeks old when the experiments were performed. The protocol for the murine CaK model was modified from a previous report [47], and described elsewhere in detail [11]. In brief, C. albicans, strain MYA-2876 (ATCC, Manassas, VA, USA), was cultured following the Shandong Eye Institute Biosafety Code.…”

Section: Ethical Statementmentioning

confidence: 99%

“…For time points that gave "0" (B) or ND (D) readings, statistical analysis was not pursued. Scale bars in (C) are 100 μm.Prompted by the identification of APCs residing in corneas [9,10], we recently demonstrated that adaptive immunity is involved in the protective mechanism against FK [11]. Specifically, using a mouse model of Candida albicans keratitis (CaK), we showed that infection of the cornea with live C. albicans blastospores not only promoted infiltration of CD4 + cells in the cornea, but also induced the formation of antibodies that counteracted fungal growth in a pathogen-specific manner, conferring an immunological memory to the mice [12,13].…”

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confidence: 99%

IL‐17 plays a central role in initiating experimental Candida albicans infection in mouse corneas

Zou

et al. 2013

Eur J Immunol

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The pathogenesis of fungal infection in the cornea remains largely unclear. To understand how the immune system influences the progression of fungal infection in corneas, we inoculated immunocompetent BALB/c mice, neutrophil-or CD4+ T-cell-depleted BALB/c mice, and nude mice with Candida albicans. We found that only immunocompetent BALB/c mice developed typical Candida keratitis (CaK), while the other mouse strains lacked obvious clinical manifestations. Furthermore, CaK development was blocked in immunocompetent mice treated with anti-IL-17A or anti-IL-23p19 to neutralize IL-17 activity. However, no significant effects were observed when Treg cells, γδ T cells, or IFN-γ were immunodepleted. Upon infection, the corneas of BALB/c mice were infiltrated with IL-17-producing leukocytes, including neutrophils and, to a lesser degree, CD4 + T cells.In contrast, leukocyte recruitment to corneas was significantly diminished in nude mice. Indeed, nude mice produced much less chemokines (e.g. CXCL1, CXCL2, CXCL10, CXCL12, CCL2, and IL-6) in response to inoculation. Remarkably, addition of CXCL2 during inoculation restored CaK induction in nude mice. In contrast to its therapeutic effect on CaK, neutralization of IL-17 exacerbated Candida-induced dermatitis in skin. We conclude that IL-17, mainly produced by neutrophils and CD4 + T cells in the corneas, is essential in the pathogenesis of CaK. Keywords: Candida albicans · Corneal infection · Fungal infection · IL-17 · NeutrophilAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionFungal infection of the cornea, namely fungal keratitis (FK), is among the main causes of blindness in many parts of the world. While the causative pathogens differ by geographic region, the most prevalent genera are Fusarium, Aspergillus, and Candida [1][2][3]. The structural characteristics of cornea (i.e. thinness and transparency) and the high proliferation rate of most initiated Correspondence: Dr. Yiqiang Wang e-mail: yiqiangwang99@hotmail.com fungi contribute to the rapid onset of FK and total loss of sight within a few days of infection. Unfortunately, many aspects of FK pathogenicity remain unclear. For example, it is not known whether the avascularity of the cornea, which affords immune and lymphangiogenic "privilege", is responsible for the rapid progression of FK [4,5]. FK progresses even after leukocytes, including neutrophils and lymphocytes, infiltrate infected cornea.Although well-documented in other organs, studies on the host-pathogen interactions in the context of FK are lacking [4][5][6]. The available data suggest an innate immune response plays a vital role in the response to fungal infection of the cornea [7,8]. Eur. J. Immunol. 2013Immunol. . 43: 2671Immunol. -2682 Figure 1. Innate resistance of nude mice to CaK induction. BALB/c mice and nude mice were inoculated with 1 × 10 5 Candida albicans blastospores. (A) The corneas were monitored under a slit lamp, and (B) evaluated with the scoring system. D...

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“…However, the in vitro model of corneal epithelium is not suitable for the research of fungal adhesion on the corneal surface, since the adherence often needs the exposed basement membrane components of damaged corneal epithelium, and the spores cannot adhere well to intact corneal surfaces in vivo [17]. Moreover, animal models of fungal keratitis always require a long time (>8 h) of eyelid closure, or scarified cornea superficially, or the injection of fungal spores directly into corneal stroma [18][19][20], whereas the adherence of fungal spores can happen within a short time, especially as the early adherence may be mediated by nonspecific physico-chemical effects [8]. Therefore, because the two above-mentioned models are not ideal for all the investigation of corneal fungal infection, it is important to construct a novel, suitable model as a supplement for the research of the early fungal adherence, on the corneal surface.…”

Section: Introductionmentioning

confidence: 99%