LPLUNC1 modulates innate immune responses to Vibrio cholerae. 2011

Ok S Shin, and Taher Uddin, and Robert Citorik, and Jennifer P Wang, and Patricia Della Pelle, and Richard L Kradin, and Colin D Bingle, and Lynne Bingle, and Andrew Camilli, and Taufiqur R Bhuiyan, and Tahmina Shirin, and Edward T Ryan, and Stephen B Calderwood, and Robert W Finberg, and Firdausi Qadri, and Regina C Larocque, and Jason B Harris
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.

BACKGROUND Recent studies demonstrate that long palate, lung, and nasal epithelium clone 1 protein (LPLUNC1) is involved in immune responses to Vibrio cholerae, and that variations in the LPLUNC1 promoter influence susceptibility to severe cholera in humans. However, no functional role for LPLUNC1 has been identified. METHODS We investigated the role of LPLUNC1 in immune responses to V. cholerae, assessing its affect on bacterial growth and killing and on innate inflammatory responses to bacterial outer membrane components, including purified lipopolysaccharide (LPS) and outer membrane vesicles. We performed immunostaining for LPLUNC1 in duodenal biopsies from cholera patients and uninfected controls. RESULTS LPLUNC1 decreased proinflammatory innate immune responses to V. cholerae and Escherichia coli LPS. The effect of LPLUNC1 was dose-dependent and occurred in a TLR4-dependent manner. LPLUNC1 did not affect lipoprotein-mediated TLR2 activation. Immunostaining demonstrated expression of LPLUNC1 in Paneth cells in cholera patients and controls. CONCLUSIONS Our results demonstrate that LPLUNC1 is expressed in Paneth cells and likely plays a role in modulating host inflammatory responses to V. cholerae infection. Attenuation of innate immune responses to LPS by LPLUNC1 may have implications for the maintenance of immune homeostasis in the intestine.

UI MeSH Term Description Entries
D007113 Immunity, Innate The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS. Immunity, Native,Immunity, Natural,Immunity, Non-Specific,Resistance, Natural,Innate Immune Response,Innate Immunity,Immune Response, Innate,Immune Responses, Innate,Immunity, Non Specific,Innate Immune Responses,Native Immunity,Natural Immunity,Natural Resistance,Non-Specific Immunity
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D004386 Duodenum The shortest and widest portion of the SMALL INTESTINE adjacent to the PYLORUS of the STOMACH. It is named for having the length equal to about the width of 12 fingers. Duodenums
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001324 Autoantigens Endogenous tissue constituents with the ability to interact with AUTOANTIBODIES and cause an immune response. Autoantigen,Autologous Antigen,Autologous Antigens,Self-Antigen,Self-Antigens,Antigen, Autologous,Antigens, Autologous,Self Antigen,Self Antigens
D014734 Vibrio cholerae The etiologic agent of CHOLERA. Bacillus cholerae,Bacillus cholerae-asiaticae,Liquidivibrio cholerae,Microspira comma,Pacinia cholerae-asiaticae,Spirillum cholerae,Spirillum cholerae-asiaticae,Vibrio albensis,Vibrio cholera,Vibrio cholerae-asiaticae,Vibrio comma
D050556 Fatty Acid-Binding Proteins Intracellular proteins that reversibly bind hydrophobic ligands including: saturated and unsaturated FATTY ACIDS; EICOSANOIDS; and RETINOIDS. They are considered a highly conserved and ubiquitously expressed family of proteins that may play a role in the metabolism of LIPIDS. Fatty Acid-Binding Protein,Adipocyte Lipid Binding Protein,Adipocyte-Specific Fatty Acid-Binding Protein,Brain-Type Fatty Acid-Binding Protein,Cytosolic Lipid-Binding Proteins,Fatty Acid-Binding Protein, Cardiac Myocyte,Fatty Acid-Binding Protein, Myocardial,Fatty Acid-Binding Proteins, Adipocyte-Specific,Fatty Acid-Binding Proteins, Brain-Specific,Fatty Acid-Binding Proteins, Cytosolic-Specific,Fatty Acid-Binding Proteins, Intestinal-Specific,Fatty Acid-Binding Proteins, Liver-Specific,Fatty Acid-Binding Proteins, Myocardial-Specific,Fatty Acid-Binding Proteins, Plasma-Membrane Specific,Intestinal Fatty Acid-Binding Protein,Liver Fatty Acid-Binding Protein,Myocardial Fatty Acid-Binding Protein,Plasma Membrane Fatty Acid-Binding Protein,Acid-Binding Protein, Fatty,Adipocyte Specific Fatty Acid Binding Protein,Brain Type Fatty Acid Binding Protein,Cytosolic Lipid Binding Proteins,Fatty Acid Binding Protein,Fatty Acid Binding Protein, Cardiac Myocyte,Fatty Acid Binding Protein, Myocardial,Fatty Acid Binding Proteins,Fatty Acid Binding Proteins, Adipocyte Specific,Fatty Acid Binding Proteins, Brain Specific,Fatty Acid Binding Proteins, Cytosolic Specific,Fatty Acid Binding Proteins, Intestinal Specific,Fatty Acid Binding Proteins, Liver Specific,Fatty Acid Binding Proteins, Myocardial Specific,Fatty Acid Binding Proteins, Plasma Membrane Specific,Intestinal Fatty Acid Binding Protein,Lipid-Binding Proteins, Cytosolic,Liver Fatty Acid Binding Protein,Myocardial Fatty Acid Binding Protein,Plasma Membrane Fatty Acid Binding Protein,Protein, Fatty Acid-Binding

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