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1.
Cell ; 167(2): 444-456.e14, 2016 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-27716507

RESUMEN

While conventional pathogenic protists have been extensively studied, there is an underappreciated constitutive protist microbiota that is an integral part of the vertebrate microbiome. The impact of these species on the host and their potential contributions to mucosal immune homeostasis remain poorly studied. Here, we show that the protozoan Tritrichomonas musculis activates the host epithelial inflammasome to induce IL-18 release. Epithelial-derived IL-18 promotes dendritic cell-driven Th1 and Th17 immunity and confers dramatic protection from mucosal bacterial infections. Along with its role as a "protistic" antibiotic, colonization with T. musculis exacerbates the development of T-cell-driven colitis and sporadic colorectal tumors. Our findings demonstrate a novel mutualistic host-protozoan interaction that increases mucosal host defenses at the cost of an increased risk of inflammatory disease.


Asunto(s)
Colitis/inmunología , Colitis/parasitología , Interacciones Huésped-Parásitos , Inflamasomas/inmunología , Mucosa Intestinal/parasitología , Microbiota/inmunología , Tricomoniasis/inmunología , Trichomonas/inmunología , Animales , Colitis/microbiología , Dientamoeba/inmunología , Inmunidad Mucosa , Interleucina-18/inmunología , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Ratones , Ratones Endogámicos C57BL , Infecciones por Salmonella/inmunología , Salmonella typhimurium/inmunología , Simbiosis , Células TH1/inmunología , Células Th17/inmunología
2.
Immunity ; 50(1): 212-224.e4, 2019 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-30650377

RESUMEN

Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal T cell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers of intestinal Th17 cells and Th2 cells and decreased numbers of RORγt+ Treg cells. Colonization with IBD microbiotas exacerbated disease in a model where colitis is induced upon transfer of naive T cells into Rag1-/- mice. The proportions of Th17 and RORγt+ Treg cells induced by each microbiota were predictive of human disease status and accounted for disease severity in the Rag1-/- colitis model. Thus, an impact on intestinal Th17 and RORγt+ Treg cell compartments emerges as a unifying feature of IBD microbiotas, suggesting a general mechanism for microbial contribution to IBD pathogenesis.


Asunto(s)
Colitis/microbiología , Microbioma Gastrointestinal/genética , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/microbiología , ARN Ribosómico 16S/genética , Linfocitos T Reguladores/inmunología , Células Th17/metabolismo , Animales , Diferenciación Celular , Colitis/inducido químicamente , Colitis/inmunología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Homeostasis , Humanos , Ratones , Ratones Endogámicos C57BL , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo
3.
Disabil Health J ; 12(2): 287-295, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30448102

RESUMEN

BACKGROUND: Increasing participation in recreational leisure activities (RLA) could be an effective vehicle for social inclusion and improvement - people's with disabilities health. Unfortunately, many barriers limit their participation in RLA. Interventions to improve access to RLA are often limited to therapeutic or adaptive sports in rehabilitation. Knowledge about the benefits of adaptive RLA in the community is still needed. OBJECTIVE/HYPOTHESIS: The aim of this study was to assess the benefits of adaptive RLA offered in the community for people with disabilities, and to document the facilitators and barriers to participation. METHODS: This paper presents the qualitative results of a mixed-methods study. The participants were members with disabilities (n = 19), volunteers (n = 9), and staff members (n = 8) of an organization offering various adaptive RLA in the community. Semi-structured interviews, focus groups, and naturalistic observations were conducted. The data were analyzed using an inductive content analysis approach. RESULTS: Three overarching themes emerged from the analysis: 1) "Personal enrichment" illustrated the individual benefits experienced by the member with disabilities; 2) "Collective impact" represented the social benefits for the members and their communities; and 3) "Contributors to the RLA experience" concerned the facilitators and barriers to participation. CONCLUSIONS: Considering the numerous benefits of adaptive RLA, it is necessary to implement specific policies to support integrated community programs or accessible public transports to allow full participation of people with disabilities, thereby increasing their social inclusion.


Asunto(s)
Integración a la Comunidad , Personas con Discapacidad/rehabilitación , Actividades Recreativas , Aislamiento Social , Participación Social , Adulto , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana Edad , Políticas , Investigación Cualitativa , Características de la Residencia
4.
Elife ; 82019 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-30666957

RESUMEN

To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn's disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).


Asunto(s)
Infecciones por Clostridium/microbiología , Enfermedad de Crohn/microbiología , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Adiposidad , Adulto , Anciano , Anciano de 80 o más Años , Animales , Clostridioides difficile , Femenino , Homeostasis , Humanos , Íleon/microbiología , Sistema Inmunológico , Enfermedades Inflamatorias del Intestino , Masculino , Ratones , Ratones Endogámicos C57BL , Microbiota , Persona de Mediana Edad , Membrana Mucosa/microbiología , Fenotipo , ARN Ribosómico 16S/metabolismo , Especificidad de la Especie , Adulto Joven
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