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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