RESUMO
Gastrointestinal nematode infections cause morbidity and socioeconomic loss in the most deprived communities. The shift in the context of obesity has led to spatial overlap with endemic gastrointestinal nematode regions resulting in the emergence of a novel comorbidity. Despite this, the impact of a high-fat diet (HFD) on immune-regulated protection against gastrointestinal infections remains largely unknown. We employed the murine model of nematode infection, Trichuris muris, to investigate the effect of an HFD on the immune response against chronic infection. Surprisingly, diet-induced obesity drove parasite expulsion in both single and repeated trickle low doses of T. muris eggs. Mechanistically, an HFD increased the expression of the ST2 receptor on CD4+ T cells, priming an enhanced type 2 helper T (Th2) cell cytokine production following interleukin (IL)-33 stimulation ex vivo. Despite IL-33-/- mice demonstrating that IL-33 is not critical for host protective immunity to T. muris under a conventional diet, HFD-fed T-cell deplete mice adoptively transferred with ST2-/- CD4 T cells were unable to expel a T. muris infection unlike those transferred with ST2-sufficient cells. Collectively, this study demonstrates that an HFD primes CD4+ T cells to utilize the IL-33-ST2 axis in a novel induction of type 2 immunity, providing insights into the emerging comorbidities of obesity and nematode infection.
Assuntos
Helmintos , Tricuríase , Camundongos , Animais , Interleucina-33 , Dieta Hiperlipídica , Proteína 1 Semelhante a Receptor de Interleucina-1 , Trichuris , Citocinas/metabolismoRESUMO
Researchers know little about whether very young children can recognize objects originally introduced to them in a picture book when they encounter similar looking objects in various real-world contexts. The present studies used an imitation procedure to explore young children's ability to generalize a novel action sequence from a picture book to novel test conditions. The authors found that 18-month-olds imitated the action sequence from a book only when the conditions at testing matched those at encoding; altering the test stimuli or context disrupted imitation (Experiment 1A). In contrast, the 24-month-olds imitated the action sequence with changes to both the test context and stimuli (Experiment 1B). Moreover, although the 24-month-olds exhibited deferred imitation with no changes to the test conditions, they did not defer imitation with changes to the context and stimuli (Experiment 2). Two factors may account for the pattern of results: age-related changes in children's ability to utilize novel retrieval cues as well as their emerging ability to understand the representational nature of pictures.