Epidemiological studies have shown that urban particulate matter (PM) increases the risk of respiratory infection. However, the underlying mechanisms are poorly understood. PM has been postulated to suppress the activation of airway epithelial innate defence in response to infection. The effects of PM on antibacterial defence were studied using an in vitro infection model. The levels of antimicrobial peptides were measured using RT-PCR and ELISA. In addition to performing colony-forming unit counts and flow cytometry, confocal microscopy was performed to directly observe bacterial invasion upon PM exposure. We found that PM PM increased bacterial invasion by impairing the induction of β-defensin-2 (hBD-2), but not the other antimicrobial peptides (APMs) secreted by airway epithelium. PM further increases bacteria-induced ROS production, which is accompanied by an accelerated cell senescence and a decrease in bacteria-induced hBD-2 production, and the antioxidant NAC treatment attenuates these effects. The PM exposure further upregulated the expression of IL-8 but downregulated the expression of IL-13 upon infection. PM promotes bacterial invasion of airway epithelial cells by attenuating the induction of hBD-2 via an oxidative burst. These findings associate PM with an increased susceptibility to infection. These findings provide insight into the underlying mechanisms regarding the pathogenesis of particulate matter.

Asthma is prone to Th2-mediated chronic airway inflammation. Interleukin-27 (IL-27) is a member of the IL-12 family that promotes the differentiation of Th1 cells and inhibits Th2 cells. We use human/mouse CD4+ T cells to see whether IL-27 could inhibit IL-4 production in vitro and then observe whether IL-27 administration could alleviate allergic airway inflammation in vivo by mice asthma model. We isolated and cultured CD4+ T cells from healthy humans and mice to test whether IL-27 could inhibit IL-4 production under different conditions. In vivo study, the effect of IL-27 was examined using two types of intra-nasal (i.n.) administration: low-dose-multiple-times prevention or high-dose-limited-times treatment in murine asthma models. The expression levels of signal transducer and activator of transcription-1 (STAT1) and growth arrest and DNA damage 45-γ (GADD45γ)/p38 mitogen activated protein kinase (p38 MAPK) in lung tissues were measured using qPCR and Western blotting. In vitro, although IL-27 could inhibit naïve CD4+ T cell differentiate into Th2 cells, but it could not redifferentiate already committed Th2 cells. In vivo, preventative administration of IL-27 attenuated allergic inflammation and airway hyperreactivity, whereas treatment group had no significant effect. In the asthma group, the phosphorylation of STAT1 was impaired, while GADD45γ and p38 MAPK exhibited no obvious changes. Preventative administration of IL-27 could either reverse the impairment of STAT1 or strengthen the expression of GADD45γ and p38 MAPK, whereas treatment group had no significant effect. Preventative administration of IL-27 improved the pathological changes in mouse asthma models via both the STAT1 and GADD45γ/p38 MAPK pathways while therapeutic administration of IL-27 had no significant effect, which may be due to the presence of already differentiated Th2 cells in asthmatic airways that resist IL-27 inhibition.

Objective: To compare the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for cryptococcosis in patients with different immune statuses with that of conventional detection.Methods: A total of 1442 specimens including 71 specimens from patients with cryptococcosis were analyzed in the study. The chi square test was used to screen the sensitivity and specificity of different detection methods for different specimen types. One-way ANOVA was used to compare the mNGS results with age, CD4, lymphocytes, IFN, IL-6, IL-2 and serum antigen assay.Results: The sensitivity of mNGS was 44.29% in Cryptococcus infection cases. The positive rate of mNGS results for bronchoalveolar lavage fluid (BALF, 87.50%) from immunocompromised patients was higher than that of BALF from immunocompetent patients (40.00%, p=0.04). The sensitivity of the serum Cryptococcus capsular antigen assay was 80.00% in immunocompetent patients and 96.42% in immunocompromised patients (p = 0.049). A positive rate of detection of Cryptococcus from mNGS was higher when cryptococcal antigen ≥1:160 (p=0.022) in immunocompromised patients. A positive rate of detection of Cryptococcus from mNGS was higher when lymphocyte counts were lower in both immunocompetent patients(p=0.017) and in immunocompromised patients(p=0.029).Conclusions: The sensitivity of mNGS is lower than that of serum cryptococcal antigen assay and histopathology in immunocompetent patients. However, BALF detection is recommend for immunocompromised patients compared with tissue and CSF. The positive mNGS result was correlated with lower lymphocyte counts, higher IL-2 and higher serum antigen assay in immunocompromised patients.

A 50-year-old woman presented with right back pain, low fever, leukocytosis, a high level of C-reactive protein and a high erythrocyte sedimentation rate. Abdominal magnetic resonance imaging (MRI) revealed a hypodense lesion in the right suprarenal region, while PET/CT showed mildly increased metabolic activity. A CT-guided percutaneous puncture was performed, and foul-smelling thick pus was removed, which indicated an anaerobic infection. A smear of the pus showed both gram-positive and gram-negative microorganisms. Traditional culture only detected Escherichia coli, Proteus mirabilis, and Actinomyces turicensis. While surprisingly, metagenomic next-generation sequencing (mNGS) of both the pus and blood showed high reads of multiple pathogens, including anaerobes and the three culture-positive pathogens. Thus, adrenal gland abscess was confirmed, and a combination therapy of catheter drainage and effective antimicrobial treatment was started. Six days later, the patient had clinically improved and mNGS showed dramatically decreased reads of all pathogens. A follow-up lab examination of inflammatory biomarkers was normal, and the adrenal mass was reduced radiographically.