Pneumocystis pneumonia (PCP) is a common opportunistic infectious disease that is prevalent in immunosuppressed hosts. Accumulating evidence shows that B cells play an important role in infectious diseases. In the present study, the immune regulatory role of mature B cells in host defense to Pneumocystis was evaluated. Pneumocystis infection resulted in a decrease in B cells in patients and mice, and the Pneumocystis burden in B cell-deficient mice also progressively increased from weeks 1 to 7 after infection. The clearance of Pneumocystis was delayed in B cell-activating factor receptor (BAFF-R)-deficient mice (BAFF-R−/− mice), which had few B cells and Pneumocystis-specific IgG and IgM antibodies, compared with clearance in wild-type (WT) mice. There were fewer effector CD4+ T cells and higher percentages of T helper (Th)1/Th17 cells in BAFF-R−/− mice than in WT mice. Adoptive transfer of naive B cells, mRNA sequencing, and IL-1β neutralization experiments indicated that IL-1β is a likely determinant of the IL-10-producing B cell-mediated suppression of Th1/Th17-cell immune responses in BAFF-R−/− PCP mice. Our data indicated that B cells play a vital role in the regulation of Th cells in response to Pneumocystis infection.

Background:Serum procalcitonin (PCT) levels differ in patients with bacterial or fungal infections and are significantly elevated in patients with Gram-negative bacteremia. We evaluated the diagnostic accuracy of different inflammatory markers to discriminate sepsis caused by different pathogens.Materials and Methods:We included 328 episodes of bacteremia from 292 patients with sepsis and 31 patients with suspected sepsis in this study. Medical records of patients who had bacteremia caused by Gram-negative bacteria (Gram-negative), Gram-positive bacteria (Gram-positive) or fungi were reviewed, and information about PCT and other inflammatory markers was recorded. The diagnostic performance of inflammatory markers was calculated via receiver operating characteristic (ROC) curves.Results:Serum PCT levels in Gram-negative, Gram-positive, and fungal sepsis were 7.47 (interquartile range [IQR]: 1.09–41.26) ng/mL, 0.48 (IQR: 0.15–2.16) ng/mL, and 0.60 (IQR: 0.14–2.06) ng/mL, respectively (P < 0.001). ROC analysis revealed an optimal cut-off value of 2.44 ng/mL for PCT in discriminating Gram-negative sepsis from Gram-positive sepsis, which yielded a sensitivity of 68.4% and a specificity of 77.1%. An optimal cut-off value of 3.11 ng/mL for PCT in discriminating Gram-negative sepsis from fungal sepsis, led to a sensitivity of 63.9% and specificity of 93.3%. Neither PCT nor other inflammatory markers could be used to distinguish between Gram-positive and fungal sepsis.Conclusion:Serum PCT levels were significantly higher in patients with Gram-negative sepsis than in those with Gram-positive or fungal sepsis. PCT is a potential sensitive biomarker for distinguishing Gram-negative sepsis from Gram-positive and fungal sepsis.

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Conventional respiratory tract specimens, such as bronchoalveolar lavage (BAL) fluid and induced sputum for diagnosing Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients are difficult to obtain. Besides, bronchoscopy is an invasive procedure that carries the risk of causing rapidly progressive respiratory insufficiency. By contrast, serum cell-free DNA (cfDNA) is easy to obtain and has been proven useful in diagnosing cancer, pregnancy associated complications, parasite infection and sepsis. In this study, we performed quantitative polymerase chain reaction (qPCR) to assess the diagnostic efficiency of using serum cfDNA, BAL fluid, and sputum DNA for PCP. Seventy-one patients (35 PCP patients and 36 non-PCP patients) were enrolled according to the clinical PCP diagnostic criteria. The sensitivity, specificity, positive predictive value, and negative predictive value of PCR using serum cfDNA were 68.6% (95% CI, 50.7–83.1), 97.2% (95% CI, 85.5–99.9), 96.0%, and 76.1%, respectively. PCR using BAL fluid and sputum had a high sensitivity (97.1% and 91.4%, respectively) but relatively low specificity (86.1% and 86.1%, respectively). The combination of the sputum PCR OR serum cfDNA PCR yielded a sensitivity of 97.1%.These results indicated that serum cfDNA might be a valuable method in PCP diagnosis.

IntroductionPneumocystis pneumonia (PCP) remains a severe complication with high mortality in immunocompromised patients. It has been well accepted that CD4+ T cells play a major role in controlling Pneumocystis infection. Th9 cells were the main source of IL-9 with multifaced roles depending on specific diseases. It is unclear whether IL-9/Th9 contributes to the immune response against PCP. The current study aims to explore the role of IL-9 and the effect of IL-9 on Th17 cells in murine model of PCP.Materials and methodsMice were intratracheally injected with 1 × 106 Pneumocystis organisms to establish the murine model of Pneumocystis infection. Pneumocystis burden was detected by TaqMan real-time PCR. Using IL-9-deficient (IL-9−/−) mice, flow cytometry, real-time PCR and enzyme-linked immunosorbent assay (ELISA) were conducted to investigate the immune function related to Th17 response in defense against Pneumocystis infection.ResultsReduced Pneumocystis burden was observed in lungs in IL-9−/− mice compared with WT mice at 3-week postinfection. IL-9−/−mice exhibited stronger Th17 immune responses than WT PCP mice through flow cytometer and real-time PCR. ELISA revealed higher levels of IL-17 and IL-23 in bronchoalveolar lavage fluid from IL-9−/− mice than WT mice. And IL-9 deficiency promoted Th17 differentiation from CD4+ naive T cells. IL-17A neutralization increased Pneumocystis burden in IL-9−/− mice.ConclusionAlthough similar basic clearance of Pneumocystis organisms was achieved in both WT and IL-9−/− PCP mice, IL-9 deficiency could lower Pneumocystis organism burden and promote pulmonary Th17 cells response in the early stage of infection.

Background. Pneumocystis pneumonia (PCP) remains a common opportunistic infection in immunosuppressed individuals. Current studies showed that multiple immune cells and cytokines took part in the host defense against Pneumocystis (PC). However, the roles of IL-17 and IL-10 in the development of PCP have not been elucidated. Methods. IL-10 and IL-17 levels in serum from PCP mice were detected via ELISA. The percentages of B10 cells, IL-10+ macrophages, and IL-10+ T cells in the lung from IL-17–/– PCP mice and Th17 cells and IL-17+γδT cells in IL-10–/– PCP mice were examined via flow cytometry. Also, antibody neutralization examination was also performed to elucidate the relationship of IL-17 and IL-10 in the PCP model. Results. We noted the increase of IL-17 and IL-10 levels in serum from mice infected with Pneumocystis. Furthermore, deficiency of IL-17 or IL-10 could lead to the delayed clearance of Pneumocystis and more severed lung damage. Our data also demonstrated that IL-17 deficiency enhanced the serum IL-10 level and the percentages of B10 cells, IL-10+ macrophages, and IL-10+ T cells in the lung from PCP mice. Interestingly, we also noted an increase of the IL-17 level in serum and Th17 cell and IL-17+γδT cell percentages in the lung from IL-10–/– PCP mice. Using antibody neutralization experiments, we found that the STAT3 gene might play a critical role in the interplay of IL-17 and IL-10 in PCP. Conclusion. Taken together, our results demonstrated that IL-17 and IL-10 could play the protective roles in the progression of PCP and the inverse correlation of them might be mediated by STAT3.

Background and Objective: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. We aimed to evaluate the temporal trends in hospitalization and mortality from acute exacerbation of COPD (AECOPD) and the associated financial costs over a 10-year period in Beijing, China. Methods: Hospital admission records from 2008 to 2017 for all patients aged ≥20 years with a primary discharge diagnosis of AECOPD were retrieved from the Beijing Public Health Information Center Database. Joinpoint regression was used to analyze trends and calculate the annual percentage change (APC) and average annual percent change (AAPC) for AECOPD hospitalization and mortality. Results: A total of 337,802 AECOPD cases were recorded from 2008 to 2017. An inverse U-shaped trend in the AECOPD hospitalization rate was observed, showing an increase from 150.2 per 100,000 inhabitants in 2008 to 218.7 per 100,000 inhabitants in 2014 (APC: 5.5%, 95% CI: 2.9-8.2), before declining to 161.13 per 100,000 inhabitants in 2017 (APC: −9.7%, 95% CI: −16.0 to-2.9). In-hospital mortality from AECOPD decreased significantly from 3.91% to 2.21% (AAPC: −11.4%, 95% CI: −15.5 to−7.0). A decline in the median length of hospital stay from 13.0 days in 2008 to 12.0 days in 2017 (P trend < 0.001) was accompanied by a decrease in the use of mechanical ventilation from 2012 to 2017 (P trend < 0.001). However, the total hospitalization cost per case increased from 15953.5 yuan (USD $2281.4) to 19874.5 yuan ($2842.1) during the same period. Conclusion: AECOPD remains a heavy burden on the health care system in Beijing. Strategies to better manage COPD and reduce hospitalizations from AECOPD are needed.

Pneumocystis is a life-threatening fungal pathogen that frequently causes fatal pneumonia (PCP) in immunocompromised individuals. Recently, B cells have been reported to play a crucial role in the pathogenesis of PCP through producing antibodies and activating CD4+ T cell response. Exosomes are nanoscale small extracellular vesicles abundant with protein cargo and can mediate immune response during infectious disease. In this study, using tandem mass tag-based quantitative proteomics coupled with bioinformatic analysis, we attempted to characterize exosomes derived from B lymphocytes in response to PCP. Several proteins were verified by parallel reaction monitoring (PRM) analysis. Also, the effects of B cell exosomes on CD4+ T cell response and phagocytic function of macrophages were clarified. Briefly, 1701 proteins were identified from B cell exosomes, and the majority of them were reported in Vesiclepedia. A total of 51 differentially expressed proteins of B cell exosomes were found in response to PCP. They were mainly associated with immune response and transcription regulation. PRM analysis confirmed the significantly changed levels of histone H1.3, vimentin, and tyrosine-protein phosphatase nonreceptor type 6 (PTPN6). Moreover, a functional study revealed the proinflammatory profile of B cell exosomes on CD4+ T cell response in PCP. Taken together, our results suggest the involvement of exosomes derived from B cells in cell-to-cell communication, providing new information on the function of B cells in response to PCP.