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Eur J Immunol ; 45(9): 2553-67, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26046550

RESUMO

Orally administrated iron is suspected to increase susceptibility to enteric infections among children in infection endemic regions. Here we investigated the effect of dietary iron on the pathology and local immune responses in intestinal infection models. Mice were held on iron-deficient, normal iron, or high iron diets and after 2 weeks they were orally challenged with the pathogen Citrobacter rodentium. Microbiome analysis by pyrosequencing revealed profound iron- and infection-induced shifts in microbiota composition. Fecal levels of the innate defensive molecules and markers of inflammation lipocalin-2 and calprotectin were not influenced by dietary iron intervention alone, but were markedly lower in mice on the iron-deficient diet after infection. Next, mice on the iron-deficient diet tended to gain more weight and to have a lower grade of colon pathology. Furthermore, survival of the nematode Caenorhabditis elegans infected with Salmonella enterica serovar Typhimurium was prolonged after iron deprivation. Together, these data show that iron limitation restricts disease pathology upon bacterial infection. However, our data also showed decreased intestinal inflammatory responses of mice fed on high iron diets. Thus additionally, our study indicates that the effects of iron on processes at the intestinal host-pathogen interface may highly depend on host iron status, immune status, and gut microbiota composition.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Infecções por Enterobacteriaceae/patologia , Mucosa Intestinal/patologia , Intestinos/patologia , Ferro da Dieta/administração & dosagem , Salmonelose Animal/metabolismo , Proteínas de Fase Aguda/biossíntese , Proteínas de Fase Aguda/imunologia , Animais , Peso Corporal/imunologia , Caenorhabditis elegans/imunologia , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/microbiologia , Citrobacter rodentium/imunologia , Dieta/métodos , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Fezes/microbiologia , Feminino , Imunidade Inata , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Intestinos/imunologia , Intestinos/microbiologia , Ferro da Dieta/efeitos adversos , Complexo Antígeno L1 Leucocitário/biossíntese , Complexo Antígeno L1 Leucocitário/imunologia , Lipocalina-2 , Lipocalinas/biossíntese , Lipocalinas/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Oncogênicas/biossíntese , Proteínas Oncogênicas/imunologia , Salmonelose Animal/imunologia , Salmonelose Animal/microbiologia , Salmonelose Animal/mortalidade , Salmonella typhimurium/imunologia , Análise de Sobrevida
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