High fat diet induced resistance to helminth infection via alternative induction of Type 2 immunity

Funjika, Evelyn and A. P. Colombo, Stefano and Hayes, Kelly S. and Tozer, Mary J and Tyrrell, Katrina A. and Cai, Shanshan and Faniyi, Aduragbemi A. and Shears, Rebecca K. and Dooley, Megan and Alshammari, Yasmine and Alhazmi, Wafaa and Assas, Mushref and Almilaibary, Abdullah and Jackson-Jones, Lucy H. and Thornton, David J. and Worthington, John J. and Grencis, Richard K. (2023) High fat diet induced resistance to helminth infection via alternative induction of Type 2 immunity. Mucosal Immunology, 16 (1). pp. 27-38. ISSN 1933-0219

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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.

Item Type:
Journal Article
Journal or Publication Title:
Mucosal Immunology
Uncontrolled Keywords:
?? helmintht-cellintestineil-33dietimmunologyimmunology and allergy ??
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Deposited On:
08 Feb 2023 14:05
Last Modified:
04 Jun 2024 10:10