Bacterial sensor triggering receptor expressed on myeloid cells-2 regulates the mucosal inflammatory response

Carmen Correale, Marco Genua, Stefania Vetrano, Elisa Mazzini, Chiara Martinoli, Antonino Spinelli, Vincenzo Arena, Laurent Peyrin-Biroulet, Flavio Caprioli, Nadia Passini, Paola Panina-Bordignon, Alessandro Repici, Alberto Malesci, Sergio Rutella, Maria Rescigno, Silvio Danese

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

BACKGROUND AND AIMS: Triggering receptor expressed on myeloid cells (TREM)-2 is a surface receptor detected on macrophages, dendritic cells, and microglia that binds repeated anionic motifs on yeast and Gram-positive and Gram-negative bacteria. Little is known about TREM-2 expression and function in the intestine or its role in inflammatory bowel disease (IBD). We investigated the expression of TREM-2 in the intestinal lamina propria and its role in the development of colonic inflammation. METHODS: We measured levels of TREM-2 in lamina propria mononuclear cells from surgical specimens collected from patients with IBD or cancer (controls). We analyzed the development of colitis in TREM-2 knockout and wild-type mice. Colon samples were isolated from mice and analyzed for cytokine expression, phagocytosis of bacteria, proliferation in colonic crypts, lamina propria mononuclear cell function, and T-cell activation by ovalbumin. RESULTS: TREM-2 was virtually absent from colon samples of control patients, but levels were significantly higher in within the inflamed mucosa of patients with IBD; it was mainly expressed by CD11c+ cells. Levels of TREM-2 increased as acute or chronic colitis was induced in mice. TREM-2 knockout mice developed less severe colitis than wild-type mice; the knockout mice lost less body weight, had a lower disease activity index, and had smaller mucosal lesions in endoscopic analysis. Colon dendritic cells from TREM-2 knockout mice produced lower levels of inflammatory cytokines and had reduced levels of bacterial killing and T-cell activation than cells from wild-type mice. CONCLUSIONS: TREM-2 contributes to mucosal inflammation during development of colitis in mice. Levels of TREM-2 are increased within the inflamed mucosa of patients with IBD, indicating its potential as a therapeutic target.

Original languageEnglish
JournalGastroenterology
Volume144
Issue number2
DOIs
Publication statusPublished - Feb 2013

Fingerprint

Myeloid Cells
Colitis
Mucous Membrane
Inflammatory Bowel Diseases
Knockout Mice
Colon
Dendritic Cells
Cytokines
Inflammation
T-Lymphocytes
Ovalbumin
Microglia
Gram-Negative Bacteria
Phagocytosis
Intestines
Yeasts
Macrophages
Body Weight
Bacteria

Keywords

  • Crohn's disease
  • Immune response
  • Mouse model
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Bacterial sensor triggering receptor expressed on myeloid cells-2 regulates the mucosal inflammatory response. / Correale, Carmen; Genua, Marco; Vetrano, Stefania; Mazzini, Elisa; Martinoli, Chiara; Spinelli, Antonino; Arena, Vincenzo; Peyrin-Biroulet, Laurent; Caprioli, Flavio; Passini, Nadia; Panina-Bordignon, Paola; Repici, Alessandro; Malesci, Alberto; Rutella, Sergio; Rescigno, Maria; Danese, Silvio.

In: Gastroenterology, Vol. 144, No. 2, 02.2013.

Research output: Contribution to journalArticle

Correale, Carmen ; Genua, Marco ; Vetrano, Stefania ; Mazzini, Elisa ; Martinoli, Chiara ; Spinelli, Antonino ; Arena, Vincenzo ; Peyrin-Biroulet, Laurent ; Caprioli, Flavio ; Passini, Nadia ; Panina-Bordignon, Paola ; Repici, Alessandro ; Malesci, Alberto ; Rutella, Sergio ; Rescigno, Maria ; Danese, Silvio. / Bacterial sensor triggering receptor expressed on myeloid cells-2 regulates the mucosal inflammatory response. In: Gastroenterology. 2013 ; Vol. 144, No. 2.
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abstract = "BACKGROUND AND AIMS: Triggering receptor expressed on myeloid cells (TREM)-2 is a surface receptor detected on macrophages, dendritic cells, and microglia that binds repeated anionic motifs on yeast and Gram-positive and Gram-negative bacteria. Little is known about TREM-2 expression and function in the intestine or its role in inflammatory bowel disease (IBD). We investigated the expression of TREM-2 in the intestinal lamina propria and its role in the development of colonic inflammation. METHODS: We measured levels of TREM-2 in lamina propria mononuclear cells from surgical specimens collected from patients with IBD or cancer (controls). We analyzed the development of colitis in TREM-2 knockout and wild-type mice. Colon samples were isolated from mice and analyzed for cytokine expression, phagocytosis of bacteria, proliferation in colonic crypts, lamina propria mononuclear cell function, and T-cell activation by ovalbumin. RESULTS: TREM-2 was virtually absent from colon samples of control patients, but levels were significantly higher in within the inflamed mucosa of patients with IBD; it was mainly expressed by CD11c+ cells. Levels of TREM-2 increased as acute or chronic colitis was induced in mice. TREM-2 knockout mice developed less severe colitis than wild-type mice; the knockout mice lost less body weight, had a lower disease activity index, and had smaller mucosal lesions in endoscopic analysis. Colon dendritic cells from TREM-2 knockout mice produced lower levels of inflammatory cytokines and had reduced levels of bacterial killing and T-cell activation than cells from wild-type mice. CONCLUSIONS: TREM-2 contributes to mucosal inflammation during development of colitis in mice. Levels of TREM-2 are increased within the inflamed mucosa of patients with IBD, indicating its potential as a therapeutic target.",
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AU - Genua, Marco

AU - Vetrano, Stefania

AU - Mazzini, Elisa

AU - Martinoli, Chiara

AU - Spinelli, Antonino

AU - Arena, Vincenzo

AU - Peyrin-Biroulet, Laurent

AU - Caprioli, Flavio

AU - Passini, Nadia

AU - Panina-Bordignon, Paola

AU - Repici, Alessandro

AU - Malesci, Alberto

AU - Rutella, Sergio

AU - Rescigno, Maria

AU - Danese, Silvio

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AB - BACKGROUND AND AIMS: Triggering receptor expressed on myeloid cells (TREM)-2 is a surface receptor detected on macrophages, dendritic cells, and microglia that binds repeated anionic motifs on yeast and Gram-positive and Gram-negative bacteria. Little is known about TREM-2 expression and function in the intestine or its role in inflammatory bowel disease (IBD). We investigated the expression of TREM-2 in the intestinal lamina propria and its role in the development of colonic inflammation. METHODS: We measured levels of TREM-2 in lamina propria mononuclear cells from surgical specimens collected from patients with IBD or cancer (controls). We analyzed the development of colitis in TREM-2 knockout and wild-type mice. Colon samples were isolated from mice and analyzed for cytokine expression, phagocytosis of bacteria, proliferation in colonic crypts, lamina propria mononuclear cell function, and T-cell activation by ovalbumin. RESULTS: TREM-2 was virtually absent from colon samples of control patients, but levels were significantly higher in within the inflamed mucosa of patients with IBD; it was mainly expressed by CD11c+ cells. Levels of TREM-2 increased as acute or chronic colitis was induced in mice. TREM-2 knockout mice developed less severe colitis than wild-type mice; the knockout mice lost less body weight, had a lower disease activity index, and had smaller mucosal lesions in endoscopic analysis. Colon dendritic cells from TREM-2 knockout mice produced lower levels of inflammatory cytokines and had reduced levels of bacterial killing and T-cell activation than cells from wild-type mice. CONCLUSIONS: TREM-2 contributes to mucosal inflammation during development of colitis in mice. Levels of TREM-2 are increased within the inflamed mucosa of patients with IBD, indicating its potential as a therapeutic target.

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