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 Harold Limper

Research output: Contribution to journalArticle

7 Scopus citations

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-γ-mediated intracellular signaling. Alveolar macrophages from Dectin-2-deficient mice (Dectin-2-/-) showed significant decreases in phospho-Syk activation after challenge with Pc cell wall components. Stimulation of Dectin-2-/- alveolar macrophages with Pc components showed significant decreases in the proinflammatory cytokines IL-6 and TNF-α. Finally, during infection with Pneumocystis murina, Dectin-2-/- mice displayed downregulated mRNA expression profiles of other CLRs implicated in fungal immunity. Although Dectin-2-/- alveolar macrophages had reduced proinflammatory cytokine release in vitro, Dectin-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 (US)
Pages (from-to)232-240
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume58
Issue number2
DOIs
StatePublished - Feb 1 2018

Keywords

  • Dectin-2
  • inflammation
  • innate immunity
  • Pneumocystis pneumonia

ASJC Scopus subject areas

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

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