Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*

The emergence of multidrug-resistant Klebsiella pneumoniae highlights the need to develop preventive measures to ameliorate Klebsiella infections. Bacteria-derived extracellular vesicles (EVs) are spherical nanometer-sized proteolipids enriched with outer membrane proteins. Gram-negative bacteria-derived EVs have gained interest for use as nonliving complex vaccines. In the present study, we evaluated whether K. pneumoniae-derived EVs confer protection against bacteria-induced lethality. K. pneumoniae-derived EVs isolated from in vitro bacterial culture supernatants induced innate immunity, including the upregulation of co-stimulatory molecule expression and proinflammatory mediator production. EV vaccination via the intraperitoneal route elicited EV-reactive antibodies and interferon-gamma-producing T-cell responses. Three vaccinations with the EVs prevented bacteria-induced lethality. As verified by sera and splenocytes adoptive transfer, the protective effect of EV vaccination was dependent on both humoral and cellular immunity. Taken together, these findings suggest that K. pneumoniae-derived EVs are a novel vaccine candidate against K. pneumoniae infections.
Animals ; Bacterial Vaccines/immunology/*microbiology/*therapeutic use ; Extracellular Vesicles/immunology/*microbiology ; Female ; Humans ; Immunity, Cellular ; Immunity, Innate ; Interferon-gamma/immunology ; Klebsiella Infections/immunology/*prevention &control ; Klebsiella pneumoniae/*immunology ; Mice, Inbred C57BL ; Vaccination

BACKGROUND/AIMS: The purpose of this study was to evaluate the value of initial C-reactive protein (CRP) as a predictor of clinical outcome and to investigate whether follow-up CRP measurement is useful for the prediction of the clinical outcome of bloodstream infections in patients with liver cirrhosis (LC), whose CRP production in response to infection may be attenuated. METHODS: A retrospective, observational study including 202 LC patients with Escherichia coli or Klebsiella pneumoniae bacteremia was conducted to assess the usefulness of serial CRP measurements in predicting clinical outcome in LC patients. The CRP ratio was defined as the ratio of the follow-up CRP level to the initial CRP level. RESULTS: The overall 30-day mortality rate of the study population was 23.8% (48/202). In the multivariate analysis, advanced age (> or = 70 years), healthcare-associated or nosocomial infections, model for end-stage liver disease (MELD) score of > or = 30, and initial body temperature of < 37degrees C were significant factors associated with mortality (all p < 0.05). No association between initial CRP level and mortality was found. In a further analysis including 87 evaluable cases who had repeated CRP measurements at day 4 and/or 5, a CRP ratio of > or = 0.7 was found to be a significant factor associated with mortality (odds ratio, 19.12; 95% confidence interval, 1.32 to 276.86; p = 0.043) after adjusting for other confounding variables. CONCLUSIONS: Initial CRP level did not predict mortality of sepsis in LC patients. However, serial CRP measurements during the first week of antimicrobial therapy may be useful as a prognostic factor for mortality in LC patients.
Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anti-Infective Agents/therapeutic use ; Bacteremia/drug therapy/*immunology/microbiology/mortality ; Biological Markers/blood ; C-Reactive Protein/*metabolism ; Chi-Square Distribution ; Escherichia coli Infections/drug therapy/*immunology/microbiology/mortality ; Female ; Humans ; Klebsiella Infections/drug therapy/*immunology/microbiology/mortality ; Klebsiella pneumoniae/*isolation & purification ; Liver Cirrhosis/complications/*immunology/mortality ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Predictive Value of Tests ; Republic of Korea ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome