Mucosal Immunity

Microbiome. 2017 Jun 23;5(1):63. doi: 10.1186/s40168-017-0278-2.

Author summary Little is known about how MAMP molecules are degraded/inactivated and how inactivating them alters the course of inflammation in vivo. Our studies demonstrate that deficiency of acyloxyacyl hydrolase (AOAH, a host enzyme that inactivates LPS), prolongs pulmonary inflammation and acute lung injury in mice challenged with LPS or Klebsiella pneumoniae. This is the strongest evidence to date that disabling a MAMP molecule promotes recovery of infection-induced tissue injury. Degradation/inactivation of MAMP molecules is especially important because alveolar macrophages, unlike macrophages in many other tissues, do not become “tolerant” when they are exposed to LPS. In other words, they lack this general mechanism for down-regulating inflammation. Our findings indicate that inactivating LPS can compensate to a large extent for this deficiency–without AOAH, the LPS- or Klebsiella-challenged mice failed to resolve acute lung injury and were more likely to die. We reported previously that persistently bioactive LPS can maintain tolerance in peritoneal macrophages for many weeks in AOAH-deficient mice. The new findings show that the inability to inactivate a MAMP has different consequences in the lungs and peritoneum, in keeping with evidence that innate immune responses are compartmentalized. Inactivation of MAMP molecules can be an important and non-redundant prerequisite for inflammation resolution.

Objective To analyze the composition of known plasmacytosis in SLE to obtain further insight into the nature of underlying mechanisms. Methods Plasmablasts of active and inactive/treated SL

Article

Author summary Alcohol use disorders (AUD) are an established risk factor for bacterial pneumonia. Further, alcohol consumption perturbs the normal intestinal microbial communities. Intestinal microbiota dysbiosis has been linked to impaired pulmonary host defense, however the role of alcohol-associated intestinal dysbiosis on pulmonary host defense is unknown. Here, we used an innovative model system to examine the role of alcohol-mediated intestinal dysbiosis on pulmonary host defense against respiratory infection with Klebsiella pneumoniae, independent of direct alcohol toxicity. We found that alcohol-mediated dysbiosis significantly increases host susceptibility to K. pneumoniae infection, independent of prevailing alcohol consumption. Alcohol-dysbiosis was associated with an altered T-cell responses in both the lung and intestinal tract following Klebsiella infection. Alcohol-dysbiosis also lead to increased pulmonary inflammation, as well as intestinal inflammation and damage. Our study demonstrates that alcohol-mediated dysbiosis impacts host defense and contributes to the impaired host defense against pneumonia frequently seen in alcohol abusers, and thus shifts conventional understanding of mechanisms of host defense impacted by alcohol. Characterization of microbial populations and metabolic products that regulate the immune system during harmful alcohol use may reveal novel therapeutic targets, as well as host-specific microbial communities that may be central to alcohol-mediated alterations in host defense.

Omeros Corporation (NASDAQ: OMER) today announced that the US Food and Drug Administration (FDA) has granted breakthrough therapy designation to OMS72

Case Rep Gastroenterol. 2017 May 19;11(2):335-343. doi: 10.1159/000475923. eCollection 2017 May-Aug.

Rationale Interleukin (IL)-33, a new member of the IL-1 family, is constitutively expressed in epithelial tissues and lymphoid organs and plays an important role in the pathogenesis of allergic disease. However, the role of IL-33 in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear.

Objective To investigate the role of IL-33 in the pathophysiology of CRSwNP.

Methods We investigated IL-33 expression and its cellular origins in the nasal polyps (NPs) of human subjects by immunohistochemistry (IHC), quantitative reverse transcription PCR (qRT-PCR), and multiplex cytokine assays. Correlations between IL-33 expression and other inflammatory markers were also explored. To investigate the role of IL-33 in CRSwNP, anti-IL-33 antibody was used in a murine model of CRS.

Results Uncinate process tissues from control (19), CRSsNP (61), CRSwNP (69) and NP tissues (71) were used in this study. Increased expression of IL-33 mRNA and protein in patients with CRSwNP compared with controls was observed. The concentration of IL-33 protein in CRSwNP was positively correlated with the number of neutrophils and the expression of several Th1 and Th17 inflammatory markers, including interferon (IFN)-γ, IL-1β, tumour necrosis factor (TNF)-α, IL-17A, IL-22, and various markers for neutrophil recruitment. However, protein levels of IL-5 and quantity of eosinophils were inversely correlated with levels of IL-33. The expression of tissue inhibitor of metalloproteinase (TIMP)-1 was negatively correlated with IL-33 protein levels, while the expression of matrix metalloproteinase (MMP)-2 and MMP-9 was positively correlated with IL-33 protein levels. In animal studies, IL-33 expression was upregulated in the CRSwNP group compared with controls. Anti-IL-33 treatment reduced the thickness of oedematous mucosa, subepithelial collagen deposition, and infiltration of neutrophils, but infiltration of eosinophils was not reduced. This treatment also inhibited the expression of neutrophilic inflammatory cytokines, but not IL-4. In addition, the expression of intracellular adhesion molecule 1, vascular adhesion molecule 1 and CXCL-2 in the nasal mucosa was suppressed in mice treated with anti-IL-33 antibody.

Conclusions Our data suggest a role for IL-33 in the pathogenesis of CRSwNP via neutrophil recruitment. Therefore, anti-IL-33 may provide a new treatment strategy to target infiltrating neutrophils in CRSwNP.

Author summary Enteric α-defensins are an ancient form of host defense against pathogens, but until recently there was no robust in vitro system available to study their functions upon secretion from the cells that produce them naturally in vivo. Here, using small intestinal enteroids as a source of naturally secreted α-defensins, we show that enteric viral infection is increased in the presence of these peptides. We then show that α-defensins also enhance infection in vivo, as predicted by the results of the enteroid model. This study points to a new role for enteric α-defensins in promoting viral infection and has implications for the ability of these peptides to dictate viral tropism in the gastrointestinal tract.

Article

IgA nephropathy patients with high levels of the biomarker may have greater risks of progression.

The human gut is home to complex microbial populations that change dynamically in response to various internal and external stimuli. The gut microbiota provides numerous functional benefits that are crucial for human health but in the setting of a disturbed equilibrium, the microbial community can cause deleterious outcomes such as diseases and cancers. Characterization of the functional activities of human gut microbiota is fundamental to understand their roles in human health and disease. Metaproteomics, which refers to the study of the entire protein collection of the microbial community in a given sample is an emerging area of research that provides informative details concerning functional aspects of the microbiota. In this mini review, we present a summary of the progress of metaproteomic analysis for studying the functional role of gut microbiota. This is followed by an overview of the experimental approaches focusing on fecal specimen for metaproteomics and is concluded by a discussion on the challenges and future directions of metaproteomic research.

Objectives: Data on adult IgA vasculitis (IgAV) are scarce. This survey was designed to better define clinical spectrum and efficacy of treatments in this population.Methods: We analyzed data fro