Mucosal Immunity

People with celiac disease may have no symptoms other than oral and dental abnormalities, such as enamel defects and recurrent aphthous ulcers. Thus, dentists and hygienists have an important role to play in identification of these patients.

Objective: Gut microbiome is considered to be involved in the pathogenesis of ankylosing spondylitis (AS). We conducted a comprehensive literature review in this area to facilitate future research.

Methods: We searched all literature in the PubMed database from inception to July .

Endometriosis is a chronic gynecological inflammatory disease characterized by the presence of functional endometrial glands and stroma outside of the uterine cavity. It affects 7–10% of women of reproductive age and up to 50% of women with infertility. The current gold standard for the diagnosis combines laparoscopic evaluation and biopsy of the visualized lesions. However, laparoscopy requires general anesthesia and developed surgical skills and it has a high procedural cost. In addition, it is associated with the risk, although rare, of potential intraoperative or postoperative complications. To date, several noninvasive biomarkers have been proposed; however, no definite diagnostic biomarker is yet available. The aim of this study was to characterize the CM proteome in patients with endometriosis using high resolution mass spectrometry—based proteomics, implemented by bioinformatic tools for quantitative analysis, in order to investigate the pathophysiological mechanisms of endometriosis. Cervical mucus samples were collected from patients affected by endometriosis and fertile controls. An aliquot of the soluble acidic fraction of each cervical mucus sample, corresponding to 0.5 mg of total protein, was left to digest with sequencing grade modified porcine trypsin. The peptides were analyzed by LC–MS/MS on a high resolution Orbitrap Elite mass spectrometer and data were evaluated using bioinformatic tools. We aimed at the first total profiling of the cervical mucus proteome in endometriosis. From the list of identified proteins, we detected a number of differentially expressed proteins, including some functionally significant proteins. Six proteins were quantitatively increased in endometriosis, almost all being involved in the inflammatory pattern. Nine proteins were quantitatively reduced in endometriosis, including some proteins related with local innate immunity (CRISP-3 and Pglyrp1) and protection against oxidative stress (HSPB1). Fifteen proteins were not detected in endometriosis samples including certain proteins involved in antimicrobial activity (SLURP1 and KLK13) and related to seminal plasma liquefaction and male fertility (KLK13). This is the first application of high resolution mass spectrometry—based proteomics aimed in detecting an array of proteins in CM to be proposed for the noninvasive diagnosis of endometriosis. This chronic disease presents in CM an inflammatory protein pattern.

Cathelicidins encompass a family of cationic peptides characterized by antimicrobial activity and other functions, such as the ability to enhance the sensing of nucleic acids by the innate immune system. The present study aimed to investigate the ability of the bovine cathelicidins Indolicidin, Bac1, Bac5, BMAP-27, BMAP-28 and BMAP-34 to inhibit the growth of bacteria and to enhance the sensing of nucleic acid by the host’s immune system. BMAP-27 was the most effective at killing Staphylococcus aureus, Streptococcus uberis and Escherichia coli, and this was dependent on its amphipathic structure and cationic charge. Although most cathelicidins possessed DNA complexing activity, only the alpha-helical BMAP cathelicidins and the cysteine-rich disulfide-bridged Bac1, were able to enhance the sensing of nucleic acids by primary epithelial cells. We also compared these responses with those mediated by neutrophils. Activation of neutrophils with phorbol myristate acetate resulted in degranulation and release of cathelicidins as well as bactericidal activity in the supernatants. However, only supernatants from unstimulated neutrophils were able to promote nucleic acid sensing in epithelial cells. Collectively, the present data supports a role for certain bovine cathelicidins in helping the innate immune system to sense nucleic acids. The latter effect is observed at concentrations clearly below those required for direct antimicrobial functions. These findings are relevant in development of future strategies to promote protection at mucosal surfaces against pathogen invasion.

Author Summary Despite significant effort, our understanding of how HIV-1 virus undermines the immune system is limited. HIV-1infection is characterized by extensive damage to intestinal mucosal barrier and translocation of bacteria and microbial products into the systemic circulation. Immune activation induced by microbial products results in chronic inflammation that drives HIV-1 pathogenesis and progression to AIDS despite successful control of HIV-1 replication by antiretroviral therapy. Here we provide evidence indicating that antibody-producing cells in the intestinal mucosa of HIV-1-infected individuals have decreased capacity to switch from the production of IgM to IgA and IgG, the types of antibodies that normally restrict the translocation of bacterial antigens across the mucosal barrier. This may facilitate systemic dissemination of microbial products and subsequent inflammation in HIV-1-infected individuals. Furthermore, the accumulation of IgM in gut mucosa may contribute to the exacerbation of inflammatory processes by the formation of inflammatory immune complexes. This newly identified dysregulation of immune system alters our understanding of HIV-1 pathogenesis and may facilitate the design of novel therapies targeting immune dysfunction in HIV-1/AIDS.