Cellular Microbiology

The aim of this study is to analyze the distribution characteristics of specific allergens based on the immunoglobulin E (IgE) test, performed using the sera of patients with allergic diseases in the Shanxi region of China. Sera from 3141 patients with allergic diseases were analyzed with immunoblotting for IgE antibodies specific to inhaled and ingested allergens. The distribution of allergens and association with factors such as disease profile, sex, age, and cosensitization of the patients who tested positive were analyzed. The most common positive rate of IgE specific to inhaled allergens was mugwort, followed by dust mite mix and common ragweed. The most common positive rate of IgE specific to ingested allergens was crab, followed by egg white and sea fish mix. When analyzed according to disease profile, mugwort was the most common allergen in asthma, rhinitis, and asthma combined with rhinitis. When analyzed by season, the allergens with the highest positive rates included tree mix (willow/poplar/elm), common ragweed, mugwort, and hop pollen from July through September. When analyzed by age, the allergens with the highest positive rates were tree mix, common ragweed, hop, house dust, cow’s milk, mutton/lamb, and peanut in participants aged 0–18 years and egg white in those aged ≥60 years. The radar charts showed cosensitization to multiple allergens. In the Shanxi region, the primary inhaled allergens were mugwort, dust mite mix (1: house dust mite/dust mite), and common ragweed. The primary ingested allergens were crab, egg white, and sea fish mix. There were differences in the positive rates of the allergens between genders, age groups, and seasons, and multiple allergens can cosensitize patients.

Ferroptosis is a new type of iron-dependent cell death caused by lipid peroxide (LPO) accumulation and involved in disease of pulmonary infection. The dysregulation of iron metabolism, the accumulation of LPO, and the inactivation and consumption of glutathione peroxidase 4 (GPX4) are the crucial cause of ferroptosis. Pulmonary infectious diseases caused by Pseudomonas aeruginosa (PA), Mycobacterium tuberculosis (MTB), and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are associated with ferroptosis. Ferroptosis may be a potential therapeutic target for pulmonary infectious diseases. However, the mechanisms by which these infections are involved in ferroptosis and whether pulmonary infectious diseases caused by Staphylococcus aureus, Klebsiella pneumoniae, and Leishmania spp are related to ferroptosis are unclear. Accordingly, more researches are needed.

Neisseria meningitidis is the most frequent cause of bacterial meningitis and is one of the few bacterial pathogens that can breach the blood-brain barrier (BBB). The 37/67 kDa laminin receptor (LamR) was previously identified as a receptor mediating meningococcal binding to rodent and human brain microvascular endothelial cells, which form part of the BBB. The meningococcal surface proteins PorA and PilQ were identified as ligands for this receptor. Subsequently, the fourth extracellular loop of PorA (PorA-Loop4) was identified as the LamR-binding moiety. Here, we show that PorA-Loop4 targets the 37 kDa laminin receptor precursor (37LRP) on the cell surface by demonstrating that deletion of this loop abrogates the recruitment of 37LRP under meningococcal colonies. Using a circularized peptide corresponding to PorA-Loop4, as well as defined meningococcal mutants, we demonstrate that host cell interaction with PorA-Loop4 results in perturbation of p-CDK4 and Cyclin D1. These changes in cell cycle control proteins are coincident with cellular responses including inhibition of cell migration and a G₁ cell cycle arrest. Modulation of the cell cycle of host cells is likely to contribute to the pathogenesis of meningococcal disease.

Objective. Smoking is a primary hazard factor for chronic obstructive pulmonary disease (COPD), which induced a decrease in intestinal Akkermansia muciniphila abundance and Th17 imbalance in COPD. This study analyzed the changes of gut microbiota metabolism and Akkermansia abundance in patients with smoking-related COPD and explored the potential function of Akkermansia muciniphila in smoke-induced COPD mice. Methods. Gut microbiota diversity and metabolic profile were analyzed by 16S rRNA sequence and metabolomics in COPD patients. The IL-1β, IL-17, TNF-α, and IL-6 levels were tested by ELISA. Lung tissue damage was observed by HE staining. The expression of cleave-caspase 3, trophoblast antigen 2 (TROP2), and LC3 in lung tissues were analyzed by IHC or IF. The p-mTOR, mTOR, p62, and LC3 expression in lung tissues were tested by western blot. Results. The levels of IL-17, IL-1β, TNF-α, and IL-6 in the peripheral blood of COPD patients increased significantly. The number and alpha diversity of gut microbiota were decreased in COPD patients. The abundance of Akkermansia muciniphila in gut of COPD patients was decreased, and the metabolic phenotype and retinol metabolism were changed. In the retinol metabolism, the retinol and retinal were significantly changed. Akkermansia muciniphila could improve the alveolar structure and inflammatory cell infiltration in lung tissue, reduce the IL-17, TNF-α, and IL-6 levels in peripheral blood, promote the p-mTOR expression, and inhibit the expression of autophagy-related proteins in smoke-induced COPD mice. Conclusion. The number and alpha diversity of gut microbiota were decreased in patients with smoking-related COPD, accompanied by decreased abundance of Akkermansia muciniphila, and altered retinol metabolism function. Gut Akkermansia muciniphila ameliorated lung injury in smoke-induced COPD mice by inflammation and autophagy.

The influenza virus induces cellular apoptosis during viral propagation, and controlling this virus-induced apoptosis process has been shown to have significant antiviral effects. The proapoptotic BH3-only protein Noxa is a strong inducer of apoptosis that can be activated by this virus, suggesting that Noxa has the potential as an anti-influenza target. To assess the value of Noxa as an antiviral target, we utilized CRISPR/Cas9 technology to produce a Noxa-knockout cell line. We found that the knockout of Noxa resulted in a dramatic reduction in the cytopathic effect induced by the influenza virus. Moreover, Noxa knockout decreased the expression of influenza viral proteins (NP, M2, HA, and NS2). In addition, Noxa deficiency triggered a complete autophagic flux to weaken influenza virus-induced autophagosome accumulation, indicating that Noxa may be a promising antiviral target for controlling influenza virus infections.

Mycobacterium avium subsp. hominissuis (M. avium) is an opportunistic environmental pathogen that typically infects patients with existing lung conditions such as cystic fibrosis or COPD. Pulmonary M. avium infection generates peribronchial granulomas that contain infected macrophages and multinucleated giant cells (MGCs). While granuloma formation with MGCs is a common feature of mycobacterial infection, the role of MGCs within the granulomas as well as in the host-pathogen interaction is poorly understood. To shed light on the role of MGCs, we established a novel in vitro model utilizing THP-1 cells stimulated with a combination of IFN-γ and TNF-α. In this study, we show that MGCs can take up M. avium, which replicates intracellularly before leaving the cell. Bacteria that escape the MGC exhibit a highly invasive phenotype, which warrants further evaluation. Characterization of MGCs with transmission electron microscopy revealed an accumulation of cytoplasmic lipid droplets, autophagic activity, and multiple nuclei. Autophagy markers are upregulated in both uninfected and infected MGCs early in infection, measured by RT-qPCR analysis of Beclin-1 and LC3. Inhibition of autophagy with siRNA significantly reduced M. avium survival significantly in THP-1 macrophages. Depletion of host cholesterol and sphingomyelin in MGCs also resulted in decreased survival of M. avium. These processes potentially contribute to the formation of a supportive intracellular environment for the pathogen. Collectively, our results suggest that M. avium is adapted to replicate in MGCs and utilize them as a springboard for local spread.