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Innate immune effectors constitute the first line of host defense against pathogens. However, the roles of these effectors are not clearly defined during Klebsiella pneumoniae (K. pneumoniae) respiratory infection. In the current study, we established an acute pneumonia model of K. pneumoniae respiratory infection in mice and confirmed that the injury was most severe 48 h post infection. Flow cytometric assay demonstrated that alveolar macrophages were the predominant cells in BALF before infection, and neutrophils were quickly recruited after infection, and this was in consistent with the kinetics of chemokine expression. Further, we depleted neutrophils, macrophages, and complement pathways in vivo and challenged these mice with a sublethal dose of K. pneumonia, the result showed that 80%, 60%, and 40% of mice were died in these groups, respectively, while no deaths occurred in the control group. Besides, innate immune effector depleted mice showed higher bacterial burdens in lungs and blood, companied with more severe lung damage and increased levels of cytokine/chemokine expression. These results demonstrated that the innate immune effectors are critical in the early controlling of K. pneumoniae infection, and neutrophils are the most important. Thus, alternative strategies targeting these innate immune effectors may be effective in controlling of K. pneumoniae respiratory infection. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a formidable pathogen that causes infections with high mortality rates. Because of its ability to form biofilms and rapidly acquire resistance to many first-line antibiotics, P. aeruginosa-related infections are typically difficult to cure by traditional antibiotic treatment regimes. Thus, new strategies to prevent and treat such infections are urgently required. PA0833 is a newly identified protective antigen of P. aeruginosa that was identified in a screen using a reverse vaccine strategy in our laboratory. In this study, we further confirmed its protective efficacy in murine sepsis and pneumonia models. Immunization with PA0833 induced strong immune responses and resulted in reduced bacterial loads; decreased pathology, inflammatory cytokine expression and inflammatory cell infiltration; and improved survival. Furthermore, PA0833 was identified as an OmpA C-like protein by bioinformatics analysis and biochemical characterization and shown to contribute to bacterial environmental stress resistance and virulence. These results demonstrate that PA0833 is an OmpA C-like protein that induces a protective immune response in mice, indicating that PA0833 is a promising antigen for vaccine development. [ABSTRACT FROM AUTHOR]

The utility of any non-rodent model system for chemical toxicity screening depends on the level of correlation between its responses and toxic reactions in rodents. Toxicity assays in the nematode Caenorhabditis elegans (C. elegans) can be fast and inexpensive; however few studies have been performed comparing toxic responses in the nematode with data on acute rodent toxicity. We assayed the acute toxicity of 21 types of chemicals in different toxicity categories using C. elegans. The nematodes were exposed to different concentrations of chemicals in 96-well plate for 24 h. The lethality rate was observed at 2, 4, 12 and 24 h, and median lethal concentration (LC50) was calculated by the Probit method. The lethality rate was counted at 1, 8, 16 and 20 h additionally at the concentrations of 10.000, 21.500 and 46.400 mg ml−1 to acquire median lethal times (LT50). The results indicated that the chemical pH could affect the C. elegans LC50 value. The pH toleration range for C. elegans was more than 2.75. Excluding 4 types of acidic chemicals, there were positive correlations between LC50s of C. elegans and LD50s of mouse/rat (r > 0.72, p < 0.01) after both 12 h and 24 h exposure. As to the LC50 data following a 24 h exposure in C. elegans, the correlation of C. elegans LC50s vs. rat LD50s (r = 0.885) was greater than the correlation of mouse vs. rat LD50s (r = 0.879), while the correlation of C. elegans LC50s vs. mouse LD50s (r = 0.741) was lower relative to that of mouse vs. rat LD50s. The data were further compared with an in vitro cytotoxicity model utilizing human epidermal keratinocytes (NHK). The data indicate that the correlation of C. elegans LC50s vs. rat LD50s was equal to the correlation of mouse vs. rat LD50s (r = 0.879), and was stronger than the correlation of NHK cell IC50s vs. rat LD50s (r = 0.844). In addition, LT50 was significantly correlative with the LC50 of C. elegans, indicating that both can be utilized as toxic effect index for further study on acute toxicity testing of chemicals. In summary, C. elegans may be a valuable model for predicting chemicals’ acute toxicity in rodents. [ABSTRACT FROM AUTHOR]