Shigella is a Gram-negative bacterium that causes bacillary dysentery worldwide. It invades the intestinal epithelium to elicit intense inflammation and tissue damage, yet the underlying mechanisms of its host selectivity and low infectious inoculum remain perplexing. Here, we report that Shigella co-opts human α-defensin 5 (HD5), a host defense peptide important for intestinal homeostasis and innate immunity, to enhance its adhesion to and invasion of mucosal tissues. HD5 promoted Shigella infection in vitro in a structure-dependent manner. Shigella, commonly devoid of an effective host-adhesion apparatus, preferentially targeted HD5 to augment its ability to colonize the intestinal epithelium through interactions with multiple bacterial membrane proteins. HD5 exacerbated infectivity and Shigella-induced pathology in a culture of human colorectal tissues and three animal models. Our findings illuminate how Shigella exploits innate immunity by turning HD5 into a virulence factor for infection, unveiling a mechanism of action for this highly proficient human pathogen.

BackgroundChronic obstructive pulmonary disease (COPD) is a progressive, irreversible chronic inflammatory disorder typified by increased recruitment of monocytes, lymphocytes and neutrophils. Because of this, as well as the convenience of peripheral blood nuclear cells (PBMCs) assessments, miRNA profiling of PBMCs has drawn increasing attention in recent years for various disease. Therefore, we analyzed miRNA and mRNA profiles to understand their regulatory network between COPD subjects versus smokers without airflow limitation.MethodsmiRNA and mRNA profiling of PBMCs from pooled 17 smokers and 14 COPD subjects was detected by high-throughput microarray. The expression of dysregulated miRNAs were validated by q-PCR. The miRNA targets in dysregulated mRNAs were predicted and the pathway enrichment was analyzed.ResultsmiRNA microarray showed that 8 miRNAs were up-regulated and 3 miRNAs were down-regulated in COPD subjects compared with smokers; the upregulation of miR-24-3p, miR-93-5p, miR-320a and miR-320b and the downregulation of miR-1273 g-3p were then validated. Bioinformatic analysis of regulatory network between miRNA and mRNA showed that NOD and TLR were the most enriched pathways. miR-24-3p was predicted to regulate IL-18, IL-1β, TNF, CCL3 and CCL4 and miR-93-5p to regulate IκBα.ConclusionsThe expression of miRNA and mRNA were dysregulated in PBMCs of COPD patients compared with smokers without airflow limitation. The regulation network between the dysregulated miRNA and mRNA may provide potential therapeutic targets for COPD.

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Human beta-defensin 3 (hBD3), an antimicrobial peptide (AMP) expressed in epithelium in response to various stimulations including human papillomavirus infection, has recently been found to be overexpressed in head and neck cancers and exhibit tumorigenic activities. However, the role of hBD3 in cervical cancer remains to be investigated. In this study, we showed by immunohistochemistry that hBD3 expression was elevated in cervical cancer samples of different stages versus the normal tissue, and was positively correlated with the progression of the disease. Overexpression of hBD3 in cervical cancer cell lines promoted cell proliferation by accelerating G1/S progression and enhanced cell migration and invasion in vitro. These oncogenic effects of hBD3 were associated with activation of NF-κB signaling. Using a mouse xenograft model, we further demonstrated that hBD3 overexpression promoted the growth of cervical cancer cells in vivo. Our results suggested that hBD3 is involved in the carcinogenesis and development of cervical cancer, and may serve as a biomarker or therapeutic target of this disease.

Pseudomonas aeruginosa is an opportunistic pathogen causing nosocomial infections in severely ill and immunocompromised patients. Ubiquitously disseminated in the environment, especially in hospitals, it has become a major threat to human health due to the constant emergence of drug-resistant strains. Multiple resistance mechanisms are exploited by P. aeruginosa, which usually result in chronic infections difficult to eradicate. Diverse virulence factors responsible for bacterial adhesion and colonization, host immune suppression, and immune escape, play important roles in the pathogenic process of P. aeruginosa. As such, antivirulence treatment that aims at reducing virulence while sparing the bacterium for its eventual elimination by the immune system, or combination therapies, has significant advantages over traditional antibiotic therapy, as the former imposes minimal selective pressure on P. aeruginosa, thus less likely to induce drug resistance. In this review, we will discuss the virulence factors of P. aeruginosa, their pathogenic roles, and recent advances in antivirulence drug discovery for the treatment of P. aeruginosa infections.