title: Colonization with Helicobacter is concomitant with modified gut microbiota and drastic failure of the immune control of Mycobacterium tuberculosis.
abstract: Epidemiological and experimental observations suggest that chronic microbial colonization can impact the immune control of other unrelated pathogens contracted in a concomitant or sequential manner. Possible interactions between Mycobacterium tuberculosis infection and persistence of other bacteria have scarcely been investigated. Here we demonstrated that natural colonization of the digestive tract with Helicobacter hepaticus in mice is concomitant with modification of the gut microbiota, subclinical inflammation, and drastic impairment of immune control of the growth of subsequently administered M. tuberculosis, which results in severe lung tissue injury. Our results provided insights upon the fact that this prior H. hepaticus colonization leads to failures in the mechanisms that could prevent the otherwise balanced cross-talk between M. tuberculosis and the immune system. Such disequilibrium ultimately leads to the inhibition of control of mycobacterial growth, outbreak of inflammation, and lung pathology. Among the dysregulated immune signatures, we noticed a correlation between the detrimental lung injury and the accumulation of activated T-lymphocytes. Our findings suggest that the impact of prior Helicobacter spp. colonization and subsequent M. tuberculosis parasitism might be greater than previously thought, which is a key point given that both species are among the most frequent invasive bacteria in human populations.
authors.affiliation: Institut Pasteur, Unité de Pathogénomique Mycobactérienne Intégrée, Paris, France.|Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris, France.|INSERM U1041, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Majlessi
authors.affiliation: Institut Pasteur, Unité de Pathogénomique Mycobactérienne Intégrée, Paris, France.|Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris, France.|INSERM U1041, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Sayes
authors.affiliation: Institut Pasteur, Unité de Génétique Fonctionnelle des Maladies Infectieuses, Paris, France.
authors.forename: J-F
authors.initials: JF
authors.lastname: Bureau
authors.affiliation: Institut Pasteur, Unité de Pathogénomique Mycobactérienne Intégrée, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Pawlik
authors.affiliation: Institut Pasteur, Unité de Pathogenèse de Helicobacter, Paris, France.|CNRS ERL3526, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Michel
authors.affiliation: Institut Pasteur, Unité d'Histopathologie Humaine et Modèles Animaux, Paris, France.|Institut Pasteur, URE Histotechnologie et Pathologie, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Jouvion
authors.affiliation: Institut Pasteur, URE Histotechnologie et Pathologie, Paris, France.|Institut Curie, Département de Pathologie, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Huerre
authors.affiliation: Institute of Biomedical Technologies, CNR, Segrate, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Severgnini
authors.affiliation: Institute of Biomedical Technologies, CNR, Segrate, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Consolandi
authors.affiliation: Institute of Biomedical Technologies, CNR, Segrate, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Peano
authors.affiliation: Institut Pasteur, Unité de Pathogénomique Mycobactérienne Intégrée, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Brosch
authors.affiliation: Institut Pasteur, Unité de Pathogenèse de Helicobacter, Paris, France.|CNRS ERL3526, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Touati
authors.affiliation: Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris, France.|INSERM U1041, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Leclerc
mesh_terms: D000818:Animals; D058491:Bacterial Load; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology*; D044923:Helicobacter hepaticus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*