Rodrigue Dessein

Publications of Rodrigue Dessein

• Bacterial modulation of Tregs/Th17 in intestinal disease: A balancing act?

  Authors: Eric Kipnis, Rodrigue Dessein

  Inflammatory bowel diseases. 11/2011;

• Defensins couple dysbiosis to primary immunodeficiency in Crohn's disease.

  Authors: Mathias Chamaillard, Rodrigue Dessein

  World journal of gastroenterology : WJG. 02/2011; 17(5):567-71.

  Antimicrobial peptides, including defensins, are essential effectors in host defence and in the maintenance of immune homeostasis. Clinical studies have linked the defective expression of both α- andAntimicrobial peptides, including defensins, are essential effectors in host defence and in the maintenance of immune homeostasis. Clinical studies have linked the defective expression of both α- and β-defensin to the reduced killing of certain microorganisms by the intestinal mucosa of patients suffering from ileal and colonic Crohn's disease (CD), respectively. Only recently have the events leading to defective expression of defensins in CD been further elucidated, and are discussed herein. These events may account for CD-associated alterations in the microbiome and may subsequently precipitate the development of granulomatous inflammatory lesions in genetically-predisposed patients. We also address how these discoveries may pave the way for the development of a molecular medicine aimed at restoring gut barrier function in CD.

• Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon.

  Authors: Laurent Peyrin-Biroulet, Julia Beisner, Guoxing Wang, Sabine Nuding, Sajit Thottathil Oommen, Denise Kelly, Erika Parmentier-Decrucq, Rodrigue Dessein, Emilie Merour, Philipe Chavatte, Teddy Grandjean, Aude Bressenot, Pierre Desreumaux, Jean-Frédéric Colombel, Béatrice Desvergne, Eduard F Stange, Jan Wehkamp, Mathias Chamaillard

  Proceedings of the National Academy of Sciences of the United States of America. 05/2010; 107(19):8772-7.

  Crohn's disease (CD), a major form of human inflammatory bowel disease, is characterized by primary immunodeficiencies. The nuclear receptor peroxisome proliferator-activated receptor gammaCrohn's disease (CD), a major form of human inflammatory bowel disease, is characterized by primary immunodeficiencies. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is essential for intestinal homeostasis in response to both dietary- and microbiota-derived signals. Its role in host defense remains unknown, however. We show that PPARgamma functions as an antimicrobial factor by maintaining constitutive epithelial expression of a subset of beta-defensin in the colon, which includes mDefB10 in mice and DEFB1 in humans. Colonic mucosa of Ppargamma mutant animals shows defective killing of several major components of the intestinal microbiota, including Candida albicans, Bacteroides fragilis, Enterococcus faecalis, and Escherichia coli. Neutralization of the colicidal activity using an anti-mDefB10 blocking antibody was effective in a PPARgamma-dependent manner. A functional promoter variant that is required for DEFB1 expression confers strong protection against Crohn's colitis and ileocolitis (odds ratio, 0.559; P = 0.018). Consistently, colonic involvement in CD is specifically linked to reduced expression of DEFB1 independent of inflammation. These findings support the development of PPARgamma-targeting therapeutic and/or nutritional approaches to prevent colonic inflammation by restoring antimicrobial immunity in CD.

• Intestinal Microbiota Gives a Nod to the Hygiene Hypothesis in Type 1 Diabetes.

  Authors: Rodrigue Dessein, Laurent Peyrin-Biroulet, Mathias Chamaillard

  Gastroenterology. 06/2009;

• TLR2 is critical for induction of REG3{beta} expression and intestinal clearance of Yersinia pseudotuberculosis.

  Authors: Rodrigue Dessein, Meritxell Gironella, Cécile Vignal, Laurent Peyrin-Biroulet, Harry Sokol, Thomas Secher, Sandra Lacas-Gervais, Jean-Jacques Gratadoux, Frank Lafont, Jean-Charles Dagorn, Bernhard Ryffel, Shizuo Akira, Philippe Langella, Gabriel Nùñez, Jean-Claude Sirard, Juan Iovanna, Michel Simonet, Mathias Chamaillard

  Gut. 02/2009;

  OBJECTIVE: Yersinia pseudotuberculosis causes ileitis and mesenteric lymphadenitis by mainly invading the Peyer's patches (PPs) that are positioned in the terminal ileum. Whereas Toll-like-receptor 2OBJECTIVE: Yersinia pseudotuberculosis causes ileitis and mesenteric lymphadenitis by mainly invading the Peyer's patches (PPs) that are positioned in the terminal ileum. Whereas Toll-like-receptor 2 (TLR2) controls mucosal inflammation by detecting certain microbiota-derived signals, its exact role in protecting PPs against bacterial invasion has not been defined. DESIGN: Wild-type, Tlr2-, Nod2- and MyD88-deficient animals were challenged by Y. pseudotuberculosis via oral or systemic route. The role of microbiota in conditioning PPs against Yersinia through TLR2 was assessed by delivering ad libitum exogenous TLR2 agonists in drinking water to Germ-Free and streptomycin-treated animals. Bacterial eradication from PPs was measured by using a colony-forming unit assay. Expression of cryptdins and the c-type lectin Reg3beta were quantified by quantitative RT-PCR. RESULTS: Our data demonstrated that Tlr2-deficient mice failed to limit Yersinia dissemination from the PPs and succumbed to sepsis independently of NOD2. Recognition of both microbiota-derived and MyD88-mediated elicitors was found to be critically involved in gut protection against Yersinia-induced lethality, while TLR2 was dispensable to systemic Yersinia infection. Gene expression analyses revealed that optimal epithelial transcript level of the anti-infective Reg3beta requires TLR2 activation. Consistently, Yersinia infection triggered TLR2-dependent Reg3beta expression in PPs. Importantly, oral treatment with exogenous TLR2 agonists in Germ-Free animals was able to further enhance Yersinia-induced expression of Reg3beta and to restore intestinal resistance to Yersinia. Lastly, genetic ablation of Reg3beta resulted in impaired clearance of the bacterial load in PPs. CONCLUSIONS: TLR2/REG3beta is thus an essential component in conditioning epithelial defense signaling pathways against bacterial invasion.

• Growth of Yersinia pseudotuberculosis in human plasma : impacts on virulence and metabolic gene expression.

  Authors: Marie-Laure Rosso, Sylvie Chauvaux, Rodrigue Dessein, Caroline Laurans, Lionel Frangeul, Celine Lacroix, Angele Schiavo, Marie-Agnes Dillies, Jeannine Foulon, Jean-Yves Coppee, Claudine Medigue, Elisabeth Carniel, Michel Simonet, Michael Marceau

  BMC microbiology. 01/2009; 8(1):211.

  ABSTRACT: BACKGROUND: In man, infection by the Gram-negative enteropathogen Yersinia pseudotuberculosis is usually limited to the terminal ileum. However, in immunocompromised patients, theABSTRACT: BACKGROUND: In man, infection by the Gram-negative enteropathogen Yersinia pseudotuberculosis is usually limited to the terminal ileum. However, in immunocompromised patients, the microorganism may disseminate from the digestive tract and thus cause a systemic infection with septicemia. RESULTS: To gain insight into the metabolic pathways and virulence factors expressed by the bacterium at the blood stage of pseudotuberculosis, we compared the overall gene transcription patterns (the transcriptome) of bacterial cells cultured in either human plasma or Luria-Bertani medium. The most marked plasma-triggered metabolic consequence in Y. pseudotuberculosis was the switch to high glucose consumption, which is reminiscent of the acetogenic pathway (known as "glucose overflow") in Escherichia coli. However, upregulation of the glyoxylate shunt enzymes suggests that (in contrast to E. coli) acetate may be further metabolized in Y. pseudotuberculosis. Our data also indicate that the bloodstream environment can regulate major virulence genes (positively or negatively); the yadA adhesin gene and most of the transcriptional units of the pYV-encoded type III secretion apparatus were found to be upregulated, whereas transcription of the pH6 antigen locus was strongly repressed. CONCLUSIONS: Our results suggest that plasma growth of Y. pseudotuberculosis is responsible for major transcriptional regulatory events and prompts key metabolic reorientations within the bacterium, which may in turn have an impact on virulence.

• Innate immunity in Crohn's disease: the reverse side of the medal.

  Authors: Rodrigue Dessein, Mathias Chamaillard, Silvio Danese

  Journal of clinical gastroenterology. 09/2008; 42 Suppl 3 Pt 1:S144-7.

  The etiology of Crohn's disease (CD) remains poorly understood. Both mice and human studies suspected a perverse link between the microbiota and the lining of the gut mucosa. There is now emergingThe etiology of Crohn's disease (CD) remains poorly understood. Both mice and human studies suspected a perverse link between the microbiota and the lining of the gut mucosa. There is now emerging evidence that suggests that such a pathologic condition might result from an overly aggressive immune response to microbial antigens in genetically predisposed individuals. However, the multiple pathophysiologic processing steps linking environmental exposure to the clinical expression of CD are, for the most part, unknown. Herein, we review evidences reflecting a general causing defect of the innate immune function of the intestinal mucosa of CD patients, which might lead to a sustained microbial-induced inflammatory response. Changing the paradigms of CD pathophysiology might lead to entirely new therapeutic approaches aiming to boost the innate immune response.

• Nod-like receptors: cytosolic watchdogs for immunity against pathogens.

  Authors: Jean-Claude Sirard, Cécile Vignal, Rodrigue Dessein, Mathias Chamaillard

  PLoS pathogens. 01/2008; 3(12):e152.

  In mammals, tissue-specific sets of pattern-recognition molecules, including Nod-like receptors (NLR), enable concomitant and sequential detection of microbial-associated molecular patterns from bothIn mammals, tissue-specific sets of pattern-recognition molecules, including Nod-like receptors (NLR), enable concomitant and sequential detection of microbial-associated molecular patterns from both the extracellular and intracellular microenvironment. Repressing and de-repressing the cytosolic surveillance machinery contributes to vital immune homeostasis and protective responses within specific tissues. Conversely, defective biology of NLR drives the development of recurrent infectious, autoimmune and/or inflammatory diseases by failing to mount barrier functions against pathogens, to tolerate commensals, and/or to instruct the adaptive immune response against microbes. Better decoding microbial strategies that are evolved to circumvent NLR sensing will provide clues for the development of rational therapies aimed at curing and/or preventing common and emerging immunopathologies.

• Prevention and treatment of colitis with Lactococcus lactis secreting the immunomodulatory Yersinia LcrV protein.

  Authors: Benoit Foligne, Rodrigue Dessein, Michael Marceau, Sabine Poiret, Mathias Chamaillard, Bruno Pot, Michel Simonet, Catherine Daniel

  Gastroenterology. 09/2007; 133(3):862-74.

  BACKGROUND & AIMS: The low calcium response V (LcrV) protein synthesized by gram-negative, pathogenic yersiniae participates in bacterial evasion of the host's innate immune response by stimulatingBACKGROUND & AIMS: The low calcium response V (LcrV) protein synthesized by gram-negative, pathogenic yersiniae participates in bacterial evasion of the host's innate immune response by stimulating synthesis of the anti-inflammatory interleukin (IL)-10 and preventing the activation of proinflammatory cytokines. METHODS: We genetically engineered the food-grade bacterium Lactococcus lactis to secrete the LcrV protein from the enteropathogenic species Yersinia pseudotuberculosis. The protective and therapeutic potential of orally administered LcrV-secreting L lactis was evaluated in 2 models of acute experimental colitis (induced by trinitrobenzene sulfonic acid [TNBS] and dextran sodium sulfate [DSS], respectively) in wild-type and knockout mice. RESULTS: Oral administration of LcrV-secreting L lactis led to active delivery of LcrV and induction of IL-10 (via a Toll-like receptor 2-dependent pathway) in the colon and prevented TNBS-induced colitis, in contrast to the L lactis control not producing LcrV. Down-regulation of tissue inflammatory markers correlated well with the reduction in damage to the colonic mucosa. In contrast, TNBS-induced colitis was not prevented in IL-10(-/-) mice pretreated with LcrV-secreting L lactis, thus showing that IL-10 is required for LcrV protection. Administration of LcrV-secreting L lactis also proved to be very effective in preventing and treating acute DSS-induced colitis. CONCLUSIONS: LcrV-secreting L lactis decreased experimentally induced intestinal inflammation in 2 murine models of colitis. This novel approach highlights the potential of using pathogen-derived immunomodulating molecules in vivo as novel therapeutics for inflammatory bowel diseases.

• Therapeutic potential of Yersinia anti-inflammatory components.

  Authors: Benoit Foligné, Rodrigue Dessein, Michaël Marceau, Sabine Poiret, Joëlle Dewulf, Bruno Pot, Michel Simonet, Catherine Daniel

  Advances in experimental medicine and biology. 02/2007; 603:361-6.

  Microbial pathogens have developed various stratagems for modulating and/or circumventing the host's innate and adaptive immunity. Hence, certain virulence factors can be viewed as potentialMicrobial pathogens have developed various stratagems for modulating and/or circumventing the host's innate and adaptive immunity. Hence, certain virulence factors can be viewed as potential therapeutic agents for human immunopathological diseases. This is the case for virulence plasmid-encoded proteins from pathogenic Yersiniae that inhibit the host's inflammatory response by interfering with various cellular signaling pathways.

• NODs in defence: from vulnerable antimicrobial peptides to chronic inflammation.

  Authors: Laurent Peyrin-Biroulet, Cécile Vignal, Rodrigue Dessein, Michel Simonet, Pierre Desreumaux, Mathias Chamaillard

  Trends in microbiology. 11/2006; 14(10):432-8.

  Defensins and cathelicidins are prevalent and essential gastrointestinal cationic antimicrobial peptides (CAPs). However, these defensive peptides are not infallible because certain enteropathogensDefensins and cathelicidins are prevalent and essential gastrointestinal cationic antimicrobial peptides (CAPs). However, these defensive peptides are not infallible because certain enteropathogens can overcome their protective function. Furthermore, impaired defensin synthesis has been linked to the occurrence of Crohn's disease (CD), a chronic inflammatory bowel disease. Recently, defective bacterial sensing through NOD1 and NOD2 has been related to reduced defensin production, CD predisposition and susceptibility to enteric infection. Hence, we propose that microbial sensors at the gut interface monitor the levels of these effector peptides, which might function as "danger" signals to confer tolerance and alert immunocytes. Further work is required to clarify how gastrointestinal CAPs are regulated and to assess their role in maintaining epithelial homeostasis and triggering adaptive immunity.

• Growth of Yersinia pseudotuberculosis in human plasma: impacts on virulence and metabolic gene expression.

  Authors: Marie-Laure Rosso, Sylvie Chauvaux, Rodrigue Dessein, Caroline Laurans, Lionel Frangeul, Céline Lacroix, Angèle Schiavo, Marie-Agnès Dillies, Jeannine Foulon, Jean-Yves Coppée, Claudine Médigue, Elisabeth Carniel, Michel Simonet, Michaël Marceau

  BMC microbiology. 8:211.

  In man, infection by the Gram-negative enteropathogen Yersinia pseudotuberculosis is usually limited to the terminal ileum. However, in immunocompromised patients, the microorganism may disseminateIn man, infection by the Gram-negative enteropathogen Yersinia pseudotuberculosis is usually limited to the terminal ileum. However, in immunocompromised patients, the microorganism may disseminate from the digestive tract and thus cause a systemic infection with septicemia.