Microbiology and Immunology最新文献

Lipopolysaccharide (LPS) is an exacerbating factor for allergic airway inflammation at least partly due to the activation of mast cells (MCs). LPS stimulates MCs to express both pro-inflammatory and type 2 cytokines, among which interleukin (IL)-13 is essential for the generation of allergic diseases. LPS also induces the expression of “alarmins” such as IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) from various cell types including epithelial cells, and increased serum IL-33 levels were reported to correlate with disease severity of asthma. MCs reside in peripheral tissues where the oxygen concentration is significantly lower than that in the air and further decreased by inflammation and bronchoconstriction in asthma. However, the effects of hypoxia on LPS-induced cytokine expression in MCs have not been fully elucidated. Here we show that LPS induces Il4, Il6, Il13, Il33, Tnf, and Tslp mRNAs in MCs. Notably, hypoxia robustly enhanced expressions of Il13 and Il33, but not the other cytokines in LPS-stimulated MCs. We also found that this promotive effect is dependent on the presence of hypoxia-inducible factor (HIF) 1α protein. Our study will provide new insight on the role of MCs in the LPS-associated pathogenesis of allergic diseases.

Human parainfluenza virus 3 (HPIV3) contains a purine-rich RNA editing site, allowing multiple viral proteins to be produced from a single gene by the posttranscriptional addition of G nucleotides. The Fukushima/O695/2019 (O695) HPIV3 clinical isolate has a G-to-A substitution at the last position of five serial G residues in the RNA editing site. This study evaluates the effects of this substitution in the RNA editing site on the biological character of HPIV3. Our results show that O695 has slightly reduced viral replication compared with viruses with an intact RNA editing site. The number of G nucleotides inserted into the RNA editing site in HPIV3 isolates with an intact RNA editing site was 5 or fewer in most cases, giving a total of 10 serial G bases (5 + 5). In contrast, the number of G nucleotides inserted into the RNA editing site in O695 showed an atypical pattern, with six or fewer in most cases. This resulted in a total of 10 (4 + 6), suggesting the additional insertion of one more nongenomic G to the mRNA of the P gene of O695 compared with viruses carrying no mutations in the RNA editing site. Phylogenetic analysis reveals that mutations in the RNA editing site occur sporadically with various mutation patterns, suggesting that these mutations are routinely selected for during the life cycle of HPIV3.

Rabies is a fatal, acute progressive encephalomyelitis caused by the rabies virus and other Lyssaviruses. Several other clinical conditions can mimic rabies. Antemortem laboratory diagnosis remains challenging and requires multiple or serial sampling for confirmation. Measurement of host-based biomarkers is an emerging area of research in infectious diseases; however, a reliable biomarker for rabies remains elusive. In this study, neurofilament light chain (NfL), an established marker of neuronal injury, has been investigated as a potential diagnostic marker for rabies. NfL levels were measured using the Simoa NfL v2 kit in serum and cerebrospinal fluid (CSF) samples received for routine diagnostic testing from encephalitis cases (rabies, n = 31; other encephalitides, n = 30) and controls (n = 24). The median serum NfL level in the rabies group was significantly higher than that in the control group (adjusted p  < 0.001), as well as the other encephalitides group (adjusted p = 0.024). Furthermore, the median CSF NfL level in the rabies group was significantly higher than that in the other encephalitides group (p < 0.001). There were no significant differences in serum or CSF NfL levels in rabies cases with different clinical presentations, prior vaccination status, or incubation period. These findings demonstrate for the first time that rabies can be differentiated from other causes of encephalitis by extremely high NfL levels.

COVID-19 severely impacts children in India, with many developing severe pneumonia or multisystem inflammatory syndrome (MIS-C). Concurrently, non-COVID-19 respiratory viruses causing community-acquired pneumonia (CAP) have resurged. These conditions present similarly, challenging accurate diagnosis. This study aims to compare inflammatory markers and clinical parameters in children with severe COVID-19 pneumonia, non-COVID-19 CAP, and COVID-associated MIS-C. We assessed 12 mediators in serum from 14 children with severe COVID-19 pneumonia, 16 with severe non-COVID-19 CAP, and 9 with MIS-C. Clinical characteristics and routine laboratory findings at admission were recorded. Children with MIS-C had significantly higher levels of IL-1RA, IL-8, and TNF compared with those with severe COVID-19 pneumonia; and higher levels of CCL2, HGF, M-CSF, and IL-8 compared with severe non-COVID-19 CAP. GROα levels tended to be higher in severe COVID-19 pneumonia. Clinical presentations were similar, but MIS-C patients had distinct laboratory findings, including lower platelet counts and albumin levels, and higher creatinine and liver enzyme levels. MIS-C exhibited a unique inflammatory profile. IL-8 emerged as a potential biomarker for MIS-C, while increased GROα levels in severe COVID-19 pneumonia merit further exploration. Combining inflammatory markers with routine laboratory parameters may improve the diagnosis and differentiation of these conditions, enhancing patient management.

Infectious mononucleosis (IM) is mainly triggered by Epstein-Barr virus (EBV) infection. There are few studies on the role of the gut microbiota in IM and EBV-associated liver dysfunction. The aim of this study was to investigate the characteristics of the gut microbiota in the EBV-associated liver dysfunction and to evaluate the relationship between the severity of gut microbiota dysbiosis and cytokine levels. A case-control study was performed. Individuals meeting the inclusion and exclusion criteria for EBV-induced IM were enrolled and their fecal and blood samples were collected. The V3-V4 region of the 16s rDNA gene of fecal microbiota was sequenced; bioinformatics analysis including α-diversity, β-diversity, and linear discriminant analysis (LDA) effect size (LEfSe) was performed; and the correlation between bacteria and clinical indices was analysed. A total of 48 participants completed fecal and blood tests, including 18 IM, 11 EBV-associated liver dysfunction, 12 healthy children and 7 EBV-negative liver dysfunction. The α-diversity and β-diversity of the gut microbiota in the EBV-associated liver dysfunction was more than that in IM. The abundance of Granulicatella, Enterococcus, Atopobium and Acinetobacter increased, while the abundance of Prevotella, Sutterella, Collinsella, Desulfovibrio decreased in the EBV-associated liver dysfunction compared with the IM. The abundance of Enterococcus, Atopobium and Acinetobacter correlated positively with the levels of IL-1β, IL-6, TNF-α and CD8⁺ cytotoxic T lymphocytes%. Gut microbiota of EBV-associated liver dysfunction was significantly disturbed and associated with systemic immune response.

Osteoarthritis (OA) is the most common joint disease and its pathogenic mechanism remains to be ensured. This study focused on the regulatory relation between B-cell lymphoma 6 (BCL6) and G-protein-coupled receptor 61 (GPR61) underlying IL-1β in OA. Real-time quantitative polymerase chain reaction and western blot were performed for mRNA and protein detection. Oxidative injury was assessed by reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) via kits. Fe²⁺ level was measured via an iron assay kit. Relation analysis between BCL6 and GPR61 was implemented employing ChIP assay and dual-luciferase reporter assay. GPR61 was downregulated in OA samples and IL-1β-induced C28/I2 cells. IL-1β-induced cell inflammation, extracellular matrix (ECM) degradation, oxidative stress, and ferroptosis were all returned by overexpression of GPR61. BCL6 downregulation was detected in OA patients and IL-1β-exposed C28/I2 cells. BCL6 could promote the transcription of GPR61. BCL6 suppressed IL-1β-induced OA progression by upregulating GPR61. The BCL6/GPR61 axis activated the PKA/CREB pathway in IL-1β-treated C28/I2 cells. The above results suggested that BCL6 mitigated OA progression induced by IL-1β by enhancing transcription of GPR61. BCL6/GPR61/PKA/CREB axis may be considered as a novel regulatory mechanism in OA, and BCL6 has the potential to act as a novel target for OA.