• The colibactin-producing <em>Escherichia coli</em> alters the tumor microenvironment to immunosuppressive lipid overload facilitating colorectal cancer progression and chemoresistance - (le 28/02/2024)

    Intratumoral bacteria flexibly contribute to cellular and molecular tumor heterogeneity for supporting cancer recurrence through poorly understood mechanisms. Using spatial metabolomic profiling technologies and 16SrRNA sequencing, we herein report that right-sided colorectal tumors are predominantly populated with Colibactin-producing Escherichia coli (CoPEC) that are locally establishing a high-glycerophospholipid microenvironment with lowered immunogenicity. It coincided with a reduced...

    • Nilmara de Oliveira Alves, Guillaume Dalmasso, Darja Nikitina, Amaury Vaysse, Richard Ruez, Lea Ledoux, Thierry Pedron, Emma Bergsten, Olivier Boulard, Lora Autier, Sofian Allam, Laurence Motreff, Pierre Sauvanet, Diane Letourneur, Pragya Kashyap, Johan Gagnière, Denis Pezet, Catherine Godfraind, Michel Salzet, Emmanuel Lemichez, Mathilde Bonnet, Imène Najjar, Christophe Malabat, Marc Monot, Denis Mestivier, Nicolas Barnich, Pankaj Yadav, Isabelle Fournier, Sean Kennedy, Amel Mettouchi, Richard Bonnet, Iradj Sobhani, Mathias Chamaillard

  • The biotherapeutic <em>Clostridium butyricum</em> MIYAIRI 588 strain potentiates enterotropism of Rorγt<sup>+</sup>Treg and PD-1 blockade efficacy - (le 22/02/2024)

    Immune checkpoint inhibitors (ICI) have been positioned as a standard of care for patients with advanced non-small-cell lung carcinomas (NSCLC). A pilot clinical trial has reflected optimistic association between supplementation with Clostridium butyricum MIYAIRI 588 (CBM588) and ICI efficacy in NSCLC. However, it remains to be established whether this biotherapeutic strain may be sufficient to heighten the immunogenicity of the tumor draining lymph nodes to overcome resistance to ICI. Herein,...

    • Thomas Paz Del Socorro, Kentaro Oka, Olivier Boulard, Motomichi Takahashi, Lionel Franz Poulin, Atsushi Hayashi, Mathias Chamaillard

  • NLRP12 interacts with NLRP3 to block the activation of the human NLRP3 inflammasome - (le 23/01/2024)

    Inflammasomes are multiprotein complexes that drive inflammation and contribute to protective immunity against pathogens and immune pathology in autoinflammatory diseases. Inflammasomes assemble when an inflammasome scaffold protein senses an activating signal and forms a signaling platform with the inflammasome adaptor protein ASC. The NLRP subfamily of NOD-like receptors (NLRs) includes inflammasome nucleators (such as NLRP3) and also NLRP12, which is genetically linked to familial...

    • Jared R Coombs, Alina Zamoshnikova, Caroline L Holley, Madhavi P Maddugoda, Daniel Eng Thiam Teo, Camille Chauvin, Lionel F Poulin, Nazarii Vitak, Connie M Ross, Manasa Mellacheruvu, Rebecca C Coll, Leonhard X Heinz, Sabrina S Burgener, Stefan Emming, Mathias Chamaillard, Dave Boucher, Kate Schroder

  • NLRP6 controls pulmonary inflammation from cigarette smoke in a gut microbiota-dependent manner - (le 26/12/2023)

    Chronic obstructive pulmonary disease (COPD) is a major health issue primarily caused by cigarette smoke (CS) and characterized by breathlessness and repeated airway inflammation. NLRP6 is a cytosolic innate receptor controlling intestinal inflammation and orchestrating the colonic host-microbial interface. However, its roles in the lungs remain largely unexplored. Using CS exposure models, our data show that airway inflammation is strongly impaired in Nlrp6-deficient mice with drastically fewer...

    • Mégane Nascimento, Sarah Huot-Marchand, Manoussa Fanny, Marjolène Straube, Marc Le Bert, Florence Savigny, Lionel Apetoh, Jacques Van Snick, Fabrice Trovero, Mathias Chamaillard, Valérie F J Quesniaux, Bernhard Ryffel, Philippe Gosset, Aurélie Gombault, Nicolas Riteau, Harry Sokol, Isabelle Couillin

  • Loss of NOD2 in macrophages improves colitis and tumorigenesis in a lysozyme-dependent manner - (le 25/10/2023)

    CONCLUSION: Our results indicate that loss of Nod2 signaling in myeloid cells aids in the tissue repair of the inflamed large intestine through lysozyme secretion by myeloid cells. These results may pave the way to design new therapeutics to limit the inflammatory and tumorigenic functions of NOD2.

    • Camille Chauvin, Katarina Radulovic, Olivier Boulard, Myriam Delacre, Nadine Waldschmitt, Paul Régnier, Gauthier Legris, Clément Bouchez, Mohamed-Yassine Sleimi, Philip Rosenstiel, Guillaume Darrasse-Jèze, Mathias Chamaillard, Lionel F Poulin

  • <em>Parvimonas micra</em>, an oral pathobiont associated with colorectal cancer, epigenetically reprograms human colonocytes - (le 16/10/2023)

    Recently, an intestinal dysbiotic microbiota with enrichment in oral cavity bacteria has been described in colorectal cancer (CRC) patients. Here, we characterize and investigate one of these oral pathobionts, the Gram-positive anaerobic coccus Parvimonas micra. We identified two phylotypes (A and B) exhibiting different phenotypes and adhesion capabilities. We observed a strong association of phylotype A with CRC, with its higher abundance in feces and in tumoral tissue compared with the normal...

    • Emma Bergsten, Denis Mestivier, Francoise Donnadieu, Thierry Pedron, Caroline Barau, Landry Tsoumtsa Meda, Amel Mettouchi, Emmanuel Lemichez, Olivier Gorgette, Mathias Chamaillard, Amaury Vaysse, Stevenn Volant, Abiba Doukani, Philippe J Sansonetti, Iradj Sobhani, Giulia Nigro

  • Activation of Nod2 signaling upon norovirus infection enhances antiviral immunity and susceptibility to colitis - (le 01/09/2023)

    Over 90% of epidemic non-bacterial gastroenteritis are caused by human noroviruses (NoVs), which persist in a substantial subset of people allowing their spread worldwide. This has led to a significant number of endemic cases and up to 70,000 children deaths in developing countries. NoVs are primarily transmitted through the fecal-oral route. To date, studies have focused on the influence of the gut microbiota on enteric viral clearance by mucosal immunity. In this study, the use of mouse...

    • Ghaffar Muharram, Marion Thépaut, Pierre-Emmanuel Lobert, Teddy Grandjean, Olivier Boulard, Myriam Delacre, Emmrich Wakeford, Richard Wheeler, Lionel Franz Poulin, Ivo Gomperts Boneca, Frank Lafont, Marie-Cécile Michallet, Didier Hober, Ken Cadwell, Mathias Chamaillard

  • NOD2 in monocytes negatively regulates macrophage development through TNFalpha - (le 07/07/2023)

    CONCLUSION: NOD2 negatively regulates a macrophage developmental program through a feed-forward loop that could be exploited for overcoming resistance to anti-TNF therapy in CD.

    • Camille Chauvin, Daniel Alvarez-Simon, Katarina Radulovic, Olivier Boulard, William Laine, Myriam Delacre, Nadine Waldschmitt, Elodie Segura, Jérome Kluza, Mathias Chamaillard, Lionel F Poulin

  • Characterisation of gut microbiota composition in patients with axial spondyloarthritis and its modulation by TNF inhibitor treatment - (le 24/03/2023)

    CONCLUSIONS: Several SpA patients' characteristics modulate the composition of gut microbiota as did TNFi treatment. Moreover, the abundance/prevalence of seven OTUs at baseline may be used as a novel non-invasive index that predicts the response to TNFi with greater accuracy than HLA-B27 status, CRP level and measures of disease activity.

    • Marie Vallier, Béatrice Segurens, Elise Larsonneur, Vincent Meyer, Stephanie Ferreira, Christophe Caloustian, Jean-François Deleuze, Maxime Dougados, Mathias Chamaillard, Corinne Miceli-Richard

  • Short- and Long-term Repercussions of Vancomycin on Immune Surveillance and the Efficacy of Antitumor Treatments - (le 23/03/2023)

    Although antibiotic is a major contributor to shifts in the intestinal flora that may persist for up to several months after cessation, it is now increasingly recognized that its prescription may differentially influence clinical outcome of different anticancer treatments. Intense clinical and basic research efforts aim then at gaining sufficient insights about how the cooperative action between the intestinal ecosystem and immune surveillance modulates the efficacy of anticancer treatments. In...

    • Thomas Paz Del Socorro, Marion Tonneau, David Pasquier, Mathias Chamaillard

  • Tirap controls Mycobacterium tuberculosis phagosomal acidification - (le 08/03/2023)

    Progression of tuberculosis is tightly linked to a disordered immune balance, resulting in inability of the host to restrict intracellular bacterial replication and its subsequent dissemination. The immune response is mainly characterized by an orchestrated recruitment of inflammatory cells secreting cytokines. This response results from the activation of innate immunity receptors that trigger downstream intracellular signaling pathways involving adaptor proteins such as the TIR-containing...

    • Imène Belhaouane, Amine Pochet, Jonathan Chatagnon, Eik Hoffmann, Christophe J Queval, Nathalie Deboosère, Céline Boidin-Wichlacz, Laleh Majlessi, Valentin Sencio, Séverine Heumel, Alexandre Vandeputte, Elisabeth Werkmeister, Laurence Fievez, Fabrice Bureau, Yves Rouillé, François Trottein, Mathias Chamaillard, Priscille Brodin, Arnaud Machelart

  • Microbe-mediated intestinal NOD2 stimulation improves linear growth of undernourished infant mice - (le 23/02/2023)

    The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain Lp^(WJL)) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that Lp^(WJL) sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from Lp^(WJL), as well as...

    • Martin Schwarzer, Umesh Kumar Gautam, Kassem Makki, Anne Lambert, Tomáš Brabec, Amélie Joly, Dagmar Šrůtková, Pierre Poinsot, Tereza Novotná, Stéphanie Geoffroy, Pascal Courtin, Petra Petr Hermanová, Renata C Matos, Jonathan J M Landry, Céline Gérard, Anne-Laure Bulteau, Tomáš Hudcovic, Hana Kozáková, Dominik Filipp, Marie-Pierre Chapot-Chartier, Marek Šinkora, Noël Peretti, Ivo Gomperts Boneca, Mathias Chamaillard, Hubert Vidal, Filipe De Vadder, François Leulier

  • The NLRP6 protein is very faintly expressed in several normal and cancerous epithelial cells and may be confused with an unrelated protein - (le 20/01/2023)

    Nod-Like Receptor Pyrin domain-containing protein 6 (NLRP6), a member of the Nucleotide-oligomerization domain-Like Receptor (NLR) family of proteins, assembles together with the ASC protein to form an inflammasome upon stimulation by bacterial lipoteichoic acid and double-stranded DNA. Besides its expression in myeloid cells, NLRP6 is also expressed in intestinal epithelial cells where it may contribute to the maintenance of gut homeostasis and negatively controls colorectal tumorigenesis....

    • Abdallah Mound, Gautier Goormachtigh, Fabrice Bray, Stéphanie Flament, Christian Rolando, Richard Ruez, Nathalie Martin, Amélie Decourcelle, Vanessa Dehennaut, Jean-Michel Saliou, Mathias Chamaillard, Corinne Abbadie

  • Use of 2,6-diaminopurine as a potent suppressor of UGA premature stop codons in cystic fibrosis - (le 15/01/2023)

    Nonsense mutations are responsible for around 10% of cases of genetic diseases, including cystic fibrosis. 2,6-diaminopurine (DAP) has recently been shown to promote efficient readthrough of UGA premature stop codons. In this study, we show that DAP can correct a nonsense mutation in the Cftr gene in vivo in a new CF mouse model, in utero, and through breastfeeding, thanks, notably, to adequate pharmacokinetic properties. DAP turns out to be very stable in plasma and is distributed throughout...

    • Catherine Leroy, Sacha Spelier, Nadège Charlene Essonghe, Virginie Poix, Rebekah Kong, Patrick Gizzi, Claire Bourban, Séverine Amand, Christine Bailly, Romain Guilbert, David Hannebique, Philippe Persoons, Gwenaëlle Arhant, Anne Prévotat, Philippe Reix, Dominique Hubert, Michèle Gérardin, Mathias Chamaillard, Natalia Prevarskaya, Sylvie Rebuffat, George Shapovalov, Jeffrey Beekman, Fabrice Lejeune

  • The extracellular matrix controls stem cell specification and crypt morphology in the developing and adult mouse gut - (le 09/11/2022)

    The rapid renewal of the epithelial gut lining is fuelled by stem cells that reside at the base of intestinal crypts. The signal transduction pathways and morphogens that regulate intestinal stem cell self-renewal and differentiation have been extensively characterised. In contrast, although extracellular matrix (ECM) components form an integral part of the intestinal stem cell niche, their direct influence on the cellular composition is less well understood. We set out to systematically compare...

    • Rana Ramadan, Valérie M Wouters, Sanne M van Neerven, Nina E de Groot, Tania Martins Garcia, Vanessa Muncan, Olivia D Franklin, Michelle Battle, Karen Sue Carlson, Joshua Leach, Owen J Sansom, Olivier Boulard, Mathias Chamaillard, Louis Vermeulen, Jan Paul Medema, David J Huels