Dataset Information

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

ABSTRACT: ?-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 ?-1,3-glucans are masked by surface proteins in Pneumocystis and what role ?-glucans play in Pneumocystis-associated inflammation. For 3 species, including Pneumocystis jirovecii, which causes Pneumocystis pneumonia in humans, Pneumocystis carinii, and Pneumocystis murina, ?-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 ?-1,3-glucan synthesis, for 21 days decreased expression of a broad panel of inflammatory markers, including interferon ?, tumor necrosis factor ?, interleukin 1?, interleukin 6, and multiple chemokines/chemokine ligands. Thus, ?-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.

SUBMITTER: Kutty G

PROVIDER: S-EPMC4978378 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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

Kutty Geetha G Davis A Sally AS Ferreyra Gabriela A GA Qiu Ju J Huang Da Wei da W Sassi Monica M Bishop Lisa L Handley Grace G Sherman Brad B Lempicki Richard R Kovacs Joseph A JA

The Journal of infectious diseases 20160619 5

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 demonstra ...[more]

PMID: 27324243

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Project description:BackgroundConcurrent infection may be found in Pneumocystis jirovecii pneumonia (PJP) of non-acquired immunodeficiency syndrome (AIDS) patients, however, its impact on immune dysregulation of PJP in non-AIDS patients remains unknown.MethodsWe measured pro-inflammatory cytokines including tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-8, IL-17, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-?1 and IL-1 receptor antagonist (IL-1RA) and inflammatory markers including high mobility group box 1, Krebs von den Lungen-6, receptor for advanced glycation end product, advanced glycation end product, surfactant protein D in bronchoalveolar lavage fluid (BALF) and blood in 47 pure PcP and 18 mixed PJP and other pulmonary infections (mixed PJP) in non-AIDS immunocompromised patients and explored their clinical relevance. The burden of Pneumocystis jirovecii in the lung was determined by counting number of clusters of Pneumocystis jirovecii per slide and the concentration of ?-D-glucan in BALF. PJP severity was determined by arterial oxygen tension/fraction of inspired oxygen concentration ratio, the need of mechanical ventilation and death.ResultsCompared with pure PJP group, mixed PJP group had significantly higher BALF levels of IL-1?, TNF-? and IL-8 and significantly higher blood levels of IL-8. The BALF ratios of TNF-?/IL-10, IL-8/IL-10, IL-1?/IL-10, TNF-?/TGF-?1, IL-8/TGF-?1, IL-1?/TGF-?1 and IL-1?/IL-1RA were significantly higher in mixed than in pure PJP patients. There was no significant difference in clinical features and outcome between pure and mixed PJP groups, including inflammatory biomarkers and the fungal burden. In pure PJP patients, significantly higher BALF levels of IL-8 and the ratios of IL-8/IL-10, IL-1?/TGF-?1, MCP-1/TGF-?1, MCP-1/IL1RA and IL-8/TGF-?1 were found in the patients requiring mechanical ventilation and in non-survivors.ConclusionsIn summary, concurrent pulmonary infection might enhance immune dysregulation of PJP in non-AIDS immunocompromised patients, but did not affect the outcome as evidenced by morbidity and mortality. Because of limited number of cases studied, further studies with larger populations are needed to verify these issues.

Dataset Information

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

Publications

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

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