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Cryptococcus neoformans in Association with Dermatophagoides pteronyssinus has Pro- (IL-6/STAT3 Overproduction) and Anti-inflammatory (CCL2/ERK1/2 Downregulation) Effects on Human Bronchial Epithelial Cells

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Abstract

Cryptococcosis (caused, for example, by Cryptococcus neoformans) and allergic asthma (caused, for example, by Dermatophagoides pteronyssinus) target the respiratory tract (the lung and bronchial epithelium). C. neoformans and D. pteronyssinus can coexist in the same indoor environment, and exposure to both can cause alterations in the local airway inflammatory milieu and exacerbation of airway inflammatory diseases. Here, we evaluated the effects of the association between C. neoformans and D. pteronyssinus in the modulation of airway inflammatory responses in an in vitro experimental model using human bronchial epithelial cells. BEAS-2B cells were cultivated and stimulated with D. pteronyssinus (10 μg/mL) and/or C. neoformans (MOI 100) for 24 h. No cytotoxic effect was observed in cells stimulated by C. neoformans and/or D. pteronyssinus. The production of IL-8, IL-6, and/or CCL2, but not IL-10, as well as the activation of NF-kB, STAT3, STAT6, and/or ERK1/2 were increased in cells stimulated by C. neoformans or D. pteronyssinus compared to controls. C. neoformans in association with D. pteronyssinus inhibited the CCL2‑ERK1/2 signaling pathway in cells treated with both pathogens compared to cells stimulated by D. pteronyssinus alone. In addition, their association induced an additive effect on the IL-6/STAT3 signaling pathway in cells compared to cells stimulated with D. pteronyssinus or C. neoformans only. D. pteronyssinus increased the internalization and growth of C. neoformans in BEAS-2B cells. D. pteronyssinus in association with C. neoformans promoted pro- and anti-inflammatory responses, which can modulate cryptococcal infection and asthmaticus status.

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Funding

This work was supported by Grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (no. 475349/2010–5), Fundação de Apoio a Pesquisa do Estado de Minas Gerais (FAPEMIG; APQ 01631/11 e APQ-01873–14), and Rede de Pesquisa em Doenças Infecciosas Humanas e Animais do Estado de Minas Gerais and Universidade Federal do Triângulo Mineiro (UFTM), Brazil. This study was also financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.

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  1. Department of Clinical Medicine, Laboratory of Experimental Immunopharmacology, Institute of Health Sciences, Federal University of Triangulo Mineiro, Uberaba, Minas Gerais, Brazil

    Henrique Ismarsi Souza, Aline Beatriz Mahler Pereira, Jhony Robison Oliveira, Paulo Roberto Silva, David Nascimento Silva Teixeira & Alexandre Paula Rogério

  2. Department of Clinical Medicine, Laboratory of Mycology, Institute of Health Sciences, Federal University of Triangulo Mineiro, Uberaba, Minas Gerais, Brazil

    Mario Leon Silva-Vergara

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Contributions

Henrique Ismarsi de Souza: data curation, formal analysis, investigation, methodology, project administration, validation, visualization, and writing—original draft preparation. Aline Beatriz Mahler Pereira: investigation, methodology, project administration, validation, visualization, and writing—original draft preparation. Jhony Robison de Oliveira: investigation and methodology. David Nascimento Silva Teixeira: funding acquisition, investigation, resources, and writing—original draft preparation. Mario Leon Silva-Vergara: funding acquisition and resources. Paulo Roberto da Silva: funding acquisition, investigation, and resources. Alexandre de Paula Rogerio: conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, supervision, validation, visualization, and writing—original draft preparation.

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Correspondence to Alexandre Paula Rogério.

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Souza, H.I., Pereira, A.B.M., Oliveira, J.R. et al. Cryptococcus neoformans in Association with Dermatophagoides pteronyssinus has Pro- (IL-6/STAT3 Overproduction) and Anti-inflammatory (CCL2/ERK1/2 Downregulation) Effects on Human Bronchial Epithelial Cells. Inflammation 45, 1269–1280 (2022). https://doi.org/10.1007/s10753-021-01619-4

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  • DOI: https://doi.org/10.1007/s10753-021-01619-4

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