Dectin-2 Is a C-Type Lectin Receptor that Recognizes Pneumocystis and Participates in Innate Immune Responses

作者：Kottom Theodore J; Hebrink Deanne M; Jenson Paige E; Marsolek Paige L; Wuthrich Marcel; Wang Huafeng; Klein Bruce; Yamasaki Sho; Limper Andrew H

来源：American Journal of Respiratory Cell and Molecular Biology, 2018, 58(2): 232-240.

DOI：10.1165/rcmb.2016-0335OC

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

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 receptorg-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-alpha. 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.

• 出版日期2018-2