IL-5 Production by Peripheral Blood Th Cells of Adult Asthma Patients in Response to &lt;i&gt;Candida albicans&lt;/i&gt; Allergen

Mori, Akio; Ikeda, Yasuko; Taniguchi, Masami; Aoyama, Chihiro; Maeda, Yuji; Hasegawa, Masato; Kimura, Noriaki; Akiyama, Kazuo

doi:10.1159/000053853

Cited by 17 publications

(13 citation statements)

References 18 publications

(23 reference statements)

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“…IL-5 is also a significant contributing cytokine to the development of asthma (47), due to its stimulation of eosinophil development (12). Others have reported IL-5 expression during C. albicans infection (6), and it is thought that C. albicans may play a role in the development of certain allergies, including asthma (26,34). Therefore, for the first time, we show the mechanism by which C. albicans induction of IL-5 could contribute to this crucial event during the development of asthma (10,17,31,38).…”

Section: Discussionmentioning

confidence: 99%

Exogenous Farnesol Interferes with the Normal Progression of Cytokine Expression during Candidiasis in a Mouse Model

Navarathna

Nickerson²,

Duhamel

et al. 2007

Infect Immun

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Candida albicans, a dimorphic fungus composed of yeast and mycelial forms, is the most common human fungal pathogen. Th1 cytokines such as interleukin-2 (IL-2), gamma interferon (IFN-␥), and tumor necrosis factor alpha (TNF-␣), which are induced by macrophage IL-12, are critical to resistance against systemic candidiasis, while Th2 cytokines such as IL-4 and IL-5 are less critical. Farnesol is a quorum-sensing molecule produced by C. albicans that controls the formation of mycelia but is also a virulence factor. To determine whether farnesol enhances the virulence of C. albicans by modulating the production of Th1 and Th2 cytokines, mice were pretreated with farnesol prior to intravenous infection with a sublethal dose of farnesol-producing C. albicans. Production of IL-2, IL-4, IL-5, TNF-␣, IFN-␥, and IL-12 was evaluated by bead-array flow cytometry and enzyme-linked immunosorbent assay. Mice exhibited an elevation in serum TNF-␣ levels at 48 h and an elevation in IFN-␥ and IL-12 levels at 6 to 12 h after infection with C. albicans. Pretreatment with farnesol significantly reduced the elevation of both IFN-␥ and IL-12 but not TNF-␣. In contrast, mice pretreated with farnesol exhibited an unexpected elevation in IL-5 levels. To determine whether farnesol has a direct effect on macrophage production of IL-12, peritoneal macrophages were pretreated with farnesol prior to stimulation with IFN-␥ plus lipopolysaccharide (LPS). Farnesol inhibited production of both IL-12 p40 and p70 from IFN-␥/LPS-stimulated macrophages. Therefore, the role of farnesol in systemic candidiasis is likely due to its ability to inhibit the critical Th1 cytokines IFN-␥ and IL-12 and perhaps to enhance a Th2 cytokine, IL-5.Candida albicans is a dimorphic commensal fungus and a medically important opportunistic pathogen, particularly in immunocompromised individuals (37). Previous work showed that yeast-mycelium dimorphism in C. albicans is regulated in part by secretion of a lipophilic molecule identified as farnesol (15). Farnesol prevents mycelial development in a quorumsensing or cell density-dependent manner, and it was the first quorum-sensing molecule (QSM) discovered in a eukaryotic organism. This work was recently reviewed by Nickerson et al. (33). However, all of the work on farnesol as a QSM has been done in vitro, leaving open the question of what role farnesol or farnesol analogs have in vivo. In this regard, Hornby et al. (15) proposed two competing hypotheses. The first was that the shift from yeast to mycelium was a critical step in pathogenesis and that exogenous farnesol could block this transition, thus acting in a therapeutic manner. The alternate hypothesis was that the lipophilic farnesol excreted during infection would interact with host cells in a manner that promoted virulence. The latter idea was supported by our work on the pathogenicity of C. albicans cells pretreated with subinhibitory concentrations (0.5 to 1 M) of fluconazole (29). These cells secreted 10 times more farnesol than did untreated cells, and they ...

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Section: Discussionmentioning

confidence: 99%

Exogenous Farnesol Interferes with the Normal Progression of Cytokine Expression during Candidiasis in a Mouse Model

Navarathna

Nickerson²,

Duhamel

et al. 2007

Infect Immun

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“…T lymphocytes in bronchoalveolar lavage from atopic asthmatic patients are activated and express increased IL-4 and IL-5 mRNA [7] and this expression correlates with airflow restriction, bronchial hyperresponsiveness and asthma severity scores [8]. PBMCs from nonatopic asthmatic individuals can produce IL-5 in response to Candida albicans, and both inhaled and skin-prick Candida challenge can elicit a late phase response in these patients [10,11]. Nonatopic patients have also been shown to produce inflammatory responses to allergen.…”

Section: Introductionmentioning

confidence: 99%

Cytokine responses of peripheral blood mononuclear cells to allergen do not identify asthma or asthma phenotypes

et al. 2013

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“…Avaliando, entretanto, por outro prisma, a eosinofilia poderia ocorrer devido à resposta imune (alérgica) tipo TH2 induzida por anticorpos IgE específicos para candida 18,19 . Colaborando com esses achados, outros estudos [19][20][21] concluíram que a resposta imune vaginal alérgica pode predispor uma candidíase crônica por indução da síntese de PGE2, que suprime a imunidade mediada por células. Fan et al 20 quantificaram IgE no fluido vaginal de mulheres com CVV e observaram maior concentração de imunoglobulina IgE em pacientes com a doença em comparação com os controles.…”

Section: Discussionunclassified

“…No entanto, Carvalho et al 22 , ao analisar anticorpos IgE específicos para candida em amostras de soro e lavado vaginal, relatou um ligeiro acréscimo nas concentrações séricas desses anticorpos em comparação com os valores encontrados em amostras vaginais, embora não tenham sido diferenças significativas. Esse fato contradiz outros resultados encontrados na literatura, sugerindo que a resposta de hipersensibilidade vaginal IgE-mediada específica para candida albicans poderia ser um cofator para vaginite recorrente em certos grupos de mulheres 20 . Apesar desses achados interessantes que demonstram uma relação de eosinofilia no sangue e associação de IgE pressupondo um quadro com substrato de reação alérgica, os resultados do presente estudo devem ser analisados dentro de suas limitações, uma vez que as pacientes não se submeteram a testes alérgicos específicos.…”

Section: Discussionunclassified

Eosinofilia no sangue periférico de mulheres com candidiase vaginal recorrente

Filho¹,

Gonçalves²,

Júnior³

et al. 2013

Rev. Bras. Ginecol. Obstet.

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ResumoOBJETIVO: Quantificar o número de células de defesa e os níveis de imunoglobulina E (IgE) no sangue periférico em amostra de mulheres com candidíase vaginal recorrente. MÉTODOS: Estudo de corte transversal com 60 mulheres, 40 com candidíase vulvovaginal e 20 do grupo controle (sem doença). As células de defesa foram identificadas utilizando um sistema de impedância combinada com a citometria de fluxo, os níveis de IgE total e específica foram medidos por meio de técnicas de quimiluminescência, o teste de Mann-Whitney foi utilizado para variáveis nominais e do teste de Spearman para correlações das concentrações de IgE e de eosinófilos no sangue periférico. RESULTADOS: O número de eosinófilos no sangue periférico de pacientes com candidíase vulvovaginal, 302,60 (±253,07), foi significativamente maior do que o grupo controle, 175,75 (±109,24) (p=0,037). Os níveis séricos de IgE total e específica foram semelhantes em ambos os grupos de mulheres com e sem candidíase vulvovaginal recorrente (p=0,361). Entretanto, observou-se uma correlação positiva moderada entre eosinofilia e níveis de IgE total no sangue periférico de mulheres com candidíase vaginal recorrente (r=0,25). CONCLUSÃO: Mulheres com candidíase vaginal recorrente parecem ter maior concentração de eosinófilos no sangue periférico que as assintomáticas. Abstract PURPOSE:To quantify the number of defense cells and immunoglobulin E (IgE) levels in peripheral blood sampled from women with recurrent vulvovaginal candidiasis. METHODS: A cross-sectional study was conducted on 60 women, 40 with vulvovaginal candidiasis and 20 controls. The defense cells were identified using an impedance system combined with flow cytometry and total and specific IgE was measured by chemiluminescence. The Mann-Whitney test was used for nominal variables and the Spearman test was used to determine the correlation of IgE concentration and eosinophils in peripheral blood. RESULTS: The number of eosinophils in peripheral blood from patients with recurrent vulvovaginal candidiasis, 302.60 (±253.07), was significantly higher compared to control, 175.75 (±109.24) (p=0.037). Serum levels of total and specific IgE were similar in the groups of women with and without recurrent vulvovaginal candidiasis (p=0.361). However, there was a moderate positive correlation between eosinophils and total serum IgE in the candidiasis group (r=0.25). CONCLUSION: Women with recurrent vulvovaginal candidiasis are more likely to have eosinophils in peripheral blood.Trabalho realizado no programa de pós-graduação em Ciências da Saúde da Universidade Federal do Rio Grande do Norte -UFRN -Natal (RN), Brasil.

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IL-5 Production by Peripheral Blood Th Cells of Adult Asthma Patients in Response to <i>Candida albicans</i> Allergen

Cited by 17 publications

References 18 publications

Exogenous Farnesol Interferes with the Normal Progression of Cytokine Expression during Candidiasis in a Mouse Model

Exogenous Farnesol Interferes with the Normal Progression of Cytokine Expression during Candidiasis in a Mouse Model

Cytokine responses of peripheral blood mononuclear cells to allergen do not identify asthma or asthma phenotypes

Eosinofilia no sangue periférico de mulheres com candidiase vaginal recorrente

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