β-Glucans Are Masked but Contribute to Pulmonary Inflammation During Pneumocystis Pneumonia

• Published in: The Journal of infectious diseases 2016-09, Vol.214 (5), p.782-791
• Main Authors: Kutty, Geetha, Davis, A. Sally, Ferreyra, Gabriela A., Qiu, Ju, Huang, Da Wei, Sassi, Monica, Bishop, Lisa, Handley, Grace, Sherman, Brad, Lempicki, Richard, Kovacs, Joseph A.
• Format: Article
• Language: English
• Subjects: Animals; Antifungal Agents - administration & dosage; beta-Glucans - immunology; Caspofungin; Cytokines - analysis; Disease Models, Animal; Echinocandins - administration & dosage; FUNGI; Lipopeptides - administration & dosage; Major and Brief Reports; Mice, Knockout; Microarray Analysis; Pneumocystis - immunology; Pneumonia - pathology; Pneumonia, Pneumocystis - microbiology; Pneumonia, Pneumocystis - pathology; Real-Time Polymerase Chain Reaction
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiw249

β-glucans, which can activate innate immune responses, are a major component in the cell wall of the cyst form of Pneumocystis. In the current study, we examined whether β-1,3-glucans are masked by surface proteins in Pneumocystis and what role β-glucans play in Pneumocystis-associated inflammation. For 3 species, including Pneumocystis jirovecii, which causes Pneumocystis pneumonia in humans, Pneumocystis carinii, and Pneumocystis murina, β-1,3-glucans were masked in most organisms, as demonstrated by increased exposure following trypsin treatment. Using quantitative polymerase chain reaction and microarray techniques, we demonstrated in a mouse model of Pneumocystis pneumonia that treatment with caspofungin, an inhibitor of β-1,3-glucan synthesis, for 21 days decreased expression of a broad panel of inflammatory markers, including interferon γ, tumor necrosis factor α, interleukin 1β, interleukin 6, and multiple chemokines/chemokine ligands. Thus, β-glucans in Pneumocystis cysts are largely masked, which likely decreases innate immune activation; this mechanism presumably was developed for interactions with immunocompetent hosts, in whom organism loads are substantially lower. In immunosuppressed hosts with a high organism burden, organism death and release of glucans appears to be an important contributor to deleterious host inflammatory responses.