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

Dectin-2 is a C-Type Lectin Receptor that Recognizes Pneumocystis and Participates in Innate Immune Responses.
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Kottom TJ, Hebrink DM, Jenson PE, Marsolek PL, Wüthrich M, Wang H, Klein B, Yamasaki S, Limper AH,


Kottom TJ, Hebrink DM, Jenson PE, Marsolek PL, Wüthrich M, Wang H, Klein B, Yamasaki S, Limper AH, (click to view)

Kottom TJ, Hebrink DM, Jenson PE, Marsolek PL, Wüthrich M, Wang H, Klein B, Yamasaki S, Limper AH,

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American journal of respiratory cell and molecular biology 2017 09 08() doi 10.1165/rcmb.2016-0335OC

Abstract

Pneumocystis remains an important fungal pathogen causing 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. Previously, a role for the CLR Dectin-1 has been 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 CRD fusions 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 proinflammatory cytokines IL-6 and TNF-α. Finally, during infection with Pneumocystis murina (Pm), Dectin-2-/- mice displayed down regulated mRNA expression profiles of other C-type Lectin Receptors (CLRs) implicated in fungal immunity. Although Dectin-2-/- alveolar macrophages had reduced proinflammatory cytokine release in vitro, Dectin-2-/- deficiency did not reduce overall resistance of these mice in the PCP model, and organism burdens were statistically similar, both in the long term immunocompromised and in short-term immunocompetent PCP models. These results suggest that Dectin-2 participates in initial innate immune signaling to Pneumocystis, but its deficiency does not impair resistance to the organism.

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