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1.
Cell Host Microbe ; 27(5): 830-840.e4, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32209431

RESUMO

The relative contributions of genetic and environmental factors to variation in immune responses are poorly understood. Here, we performed a phenotypic analysis of immunological parameters in laboratory mice carrying susceptibility genes implicated in inflammatory bowel disease (IBD) (Nod2 and Atg16l1) upon exposure to environmental microbes. Mice were released into an outdoor enclosure (rewilded) and then profiled for immune responses in the blood and lymph nodes. Variations of immune cell populations were largely driven by the environment, whereas cytokine production elicited by microbial antigens was more affected by the genetic mutations. We identified transcriptional signatures in the lymph nodes associated with differences in T cell populations. Subnetworks associated with responses against Clostridium perfringens, Candida albicans, and Bacteroides vulgatus were also coupled with rewilding. Therefore, exposing laboratory mice with genetic mutations to a natural environment uncovers different contributions to variations in microbial responses and immune cell composition.


Assuntos
Doenças Inflamatórias Intestinais , Animais , Proteínas Relacionadas à Autofagia , Bacteroides , Proteínas de Transporte , Meio Ambiente , Camundongos
2.
Cell Host Microbe ; 27(5): 809-822.e6, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32209432

RESUMO

Free-living mammals, such as humans and wild mice, display heightened immune activation compared with artificially maintained laboratory mice. These differences are partially attributed to microbial exposure as laboratory mice infected with pathogens exhibit immune profiles more closely resembling that of free-living animals. Here, we examine how colonization by microorganisms within the natural environment contributes to immune system maturation by releasing inbred laboratory mice into an outdoor enclosure. In addition to enhancing differentiation of T cell populations previously associated with pathogen exposure, outdoor release increased circulating granulocytes. However, these "rewilded" mice were not infected by pathogens previously implicated in immune activation. Rather, immune system changes were associated with altered microbiota composition with notable increases in intestinal fungi. Fungi isolated from rewilded mice were sufficient in increasing circulating granulocytes. These findings establish a model to investigate how the natural environment impacts immune development and show that sustained fungal exposure impacts granulocyte numbers.


Assuntos
Meio Ambiente , Fungos/crescimento & desenvolvimento , Fungos/fisiologia , Microbioma Gastrointestinal/imunologia , Animais , Proteínas Relacionadas à Autofagia/genética , Linfócitos T CD8-Positivos , Fezes/microbiologia , Feminino , Fungos/genética , Fungos/isolamento & purificação , Granulócitos/imunologia , Sistema Imunitário , Intestinos/microbiologia , Intestinos/patologia , Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Micobioma/imunologia , Micobioma/fisiologia , Proteína Adaptadora de Sinalização NOD2/genética
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