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 language | English (US) |
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Pages (from-to) | 232-240 |
Number of pages | 9 |
Journal | American journal of respiratory cell and molecular biology |
Volume | 58 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2018 |
Keywords
- Dectin-2
- Inflammation
- Innate immunity
- Pneumocystis pneumonia
ASJC Scopus subject areas
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry
- Cell Biology