title: LPLUNC1 modulates innate immune responses to Vibrio cholerae.
abstract: 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.
authors: Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
authors: Ok S
authors: OS
authors: Shin
authors: Taher
authors: T
authors: Uddin
authors: Robert
authors: R
authors: Citorik
authors: Jennifer P
authors: JP
authors: Wang
authors: Patricia
authors: P
authors: Della Pelle
authors: Richard L
authors: RL
authors: Kradin
authors: Colin D
authors: CD
authors: Bingle
authors: Lynne
authors: L
authors: Bingle
authors: Andrew
authors: A
authors: Camilli
authors: Taufiqur R
authors: TR
authors: Bhuiyan
authors: Tahmina
authors: T
authors: Shirin
authors: Edward T
authors: ET
authors: Ryan
authors: Stephen B
authors: SB
authors: Calderwood
authors: Robert W
authors: RW
authors: Finberg
authors: Firdausi
authors: F
authors: Qadri
authors: Regina C
authors: RC
authors: Larocque
authors: Jason B
authors: JB
authors: Harris
mesh_terms: D001324:Autoantigens; D004386:Duodenum / Q000276:immunology / Q000473:pathology; D004926:Escherichia coli / Q000276:immunology; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000276:immunology*; D019879:Paneth Cells / Q000276:immunology; D011506:Proteins / Q000276:immunology*; D014734:Vibrio cholerae / Q000276:immunology*
chemical_list: D001324:Autoantigens; C568077:BPIFB1 protein, human; D050556:Fatty Acid-Binding Proteins; D008070:Lipopolysaccharides; D011506:Proteins