Dectin-2 is a C-type lectin receptor that recognizes pneumocystis and participates in innate immune responses

Theodore J. Kottom, Deanne M. Hebrink, Paige E. Jenson, Paige L. Marsolek, Marcel Wüthrich, Huafeng Wang, Bruce Klein, Sho Yamasaki, Andrew H. Limper

    Research output: Contribution to journalEditorial

    6 Citations (Scopus)

    Abstract

    Pneumocystis is an important fungal pathogen that causes life-threatening pneumonia in patients with AIDS and malignancy. Lung fungal pathogens are recognized by C-type lectin receptors (CLRs), which bind specific ligands and stimulate innate immune responses. The CLR Dectin-1 was previously shown to mediate immune responses to Pneumocystis spp. For this reason, we investigated a potential role for Dectin-2. Rats with Pneumocystis pneumonia (PCP) exhibited elevated Dectin-2 mRNA levels. Soluble Dectin-2 carbohydrate-recognition domain fusion protein showed binding to intact Pneumocystis carinii (Pc) and to native Pneumocystis major surface glycoprotein/glycoprotein A (Msg/gpA). RAW macrophage cells expressing V5-tagged Dectin-2 displayed enhanced binding to Pc and increased protein tyrosine phosphorylation. Furthermore, the binding of Pc to Dectin-2 resulted in Fc receptor-g-mediated intracellular signaling. Alveolar macrophages from Dectin-2-deficient mice (Dectin-22/2) showed significant decreases in phospho-Syk activation after challenge with Pc cell wall components. Stimulation of Dectin-22/2 alveolar macrophages with Pc components showed significant decreases in the proinflammatory cytokines IL-6 and TNF-a. Finally, during infection with Pneumocystis murina, Dectin-22/2 mice displayed downregulated mRNA expression profiles of other CLRs implicated in fungal immunity. Although Dectin-22/2 alveolar macrophages had reduced proinflammatory cytokine release in vitro, Dectin-22/2 deficiency did not reduce the overall resistance of these mice in the PCP model, and organism burdens were statistically similar in the long-term immunocompromised and short-term immunocompetent PCP models. These results suggest that Dectin-2 participates in the initial innate immune signaling response to Pneumocystis, but its deficiency does not impair resistance to the organism.

    Original languageEnglish
    Pages (from-to)232-240
    Number of pages9
    JournalAmerican journal of respiratory cell and molecular biology
    Volume58
    Issue number2
    DOIs
    Publication statusPublished - Feb 2018

    Fingerprint

    Pneumocystis
    C-Type Lectins
    Innate Immunity
    Pneumocystis carinii
    Pathogens
    Pneumocystis Pneumonia
    Alveolar Macrophages
    Cells
    Cytokines
    Messenger RNA
    Phosphorylation
    Fc Receptors
    Macrophages
    Membrane Glycoproteins
    mouse dectin-2
    Tyrosine
    Rats
    Interleukin-6
    Pneumocystis Infections
    Glycoproteins

    All Science Journal Classification (ASJC) codes

    • Molecular Biology
    • Pulmonary and Respiratory Medicine
    • Clinical Biochemistry
    • Cell Biology

    Cite this

    Dectin-2 is a C-type lectin receptor that recognizes pneumocystis and participates in innate immune responses. / Kottom, Theodore J.; Hebrink, Deanne M.; Jenson, Paige E.; Marsolek, Paige L.; Wüthrich, Marcel; Wang, Huafeng; Klein, Bruce; Yamasaki, Sho; Limper, Andrew H.

    In: American journal of respiratory cell and molecular biology, Vol. 58, No. 2, 02.2018, p. 232-240.

    Research output: Contribution to journalEditorial

    Kottom, TJ, Hebrink, DM, Jenson, PE, Marsolek, PL, Wüthrich, M, Wang, H, Klein, B, Yamasaki, S & Limper, AH 2018, 'Dectin-2 is a C-type lectin receptor that recognizes pneumocystis and participates in innate immune responses', American journal of respiratory cell and molecular biology, vol. 58, no. 2, pp. 232-240. https://doi.org/10.1165/rcmb.2016-0186OC
    Kottom, Theodore J. ; Hebrink, Deanne M. ; Jenson, Paige E. ; Marsolek, Paige L. ; Wüthrich, Marcel ; Wang, Huafeng ; Klein, Bruce ; Yamasaki, Sho ; Limper, Andrew H. / Dectin-2 is a C-type lectin receptor that recognizes pneumocystis and participates in innate immune responses. In: American journal of respiratory cell and molecular biology. 2018 ; Vol. 58, No. 2. pp. 232-240.
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    abstract = "Pneumocystis is an important fungal pathogen that causes life-threatening pneumonia in patients with AIDS and malignancy. Lung fungal pathogens are recognized by C-type lectin receptors (CLRs), which bind specific ligands and stimulate innate immune responses. The CLR Dectin-1 was previously shown to mediate immune responses to Pneumocystis spp. For this reason, we investigated a potential role for Dectin-2. Rats with Pneumocystis pneumonia (PCP) exhibited elevated Dectin-2 mRNA levels. Soluble Dectin-2 carbohydrate-recognition domain fusion protein showed binding to intact Pneumocystis carinii (Pc) and to native Pneumocystis major surface glycoprotein/glycoprotein A (Msg/gpA). RAW macrophage cells expressing V5-tagged Dectin-2 displayed enhanced binding to Pc and increased protein tyrosine phosphorylation. Furthermore, the binding of Pc to Dectin-2 resulted in Fc receptor-g-mediated intracellular signaling. Alveolar macrophages from Dectin-2-deficient mice (Dectin-22/2) showed significant decreases in phospho-Syk activation after challenge with Pc cell wall components. Stimulation of Dectin-22/2 alveolar macrophages with Pc components showed significant decreases in the proinflammatory cytokines IL-6 and TNF-a. Finally, during infection with Pneumocystis murina, Dectin-22/2 mice displayed downregulated mRNA expression profiles of other CLRs implicated in fungal immunity. Although Dectin-22/2 alveolar macrophages had reduced proinflammatory cytokine release in vitro, Dectin-22/2 deficiency did not reduce the overall resistance of these mice in the PCP model, and organism burdens were statistically similar in the long-term immunocompromised and short-term immunocompetent PCP models. These results suggest that Dectin-2 participates in the initial innate immune signaling response to Pneumocystis, but its deficiency does not impair resistance to the organism.",
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    AU - Wüthrich, Marcel

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    AU - Klein, Bruce

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