2. Academic Validation
  3. An IFNγ-dependent immune-endocrine circuit lowers blood glucose to potentiate the innate antiviral immune response

An IFNγ-dependent immune-endocrine circuit lowers blood glucose to potentiate the innate antiviral immune response

  • Nat Immunol. 2024 Jun;25(6):981-993. doi: 10.1038/s41590-024-01848-3.
Marko Šestan # 1 2,  Sanja Mikašinović # 1,  Ante Benić 1,  Stephan Wueest 3,  Christoforos Dimitropoulos 4,  Karlo Mladenić 1,  Mia Krapić 1,  Lea Hiršl 5,  Yossef Glantzspiegel 6,  Ana Rasteiro 2,  Maria Aliseychik 2,  Đurđica Cekinović Grbeša 7,  Tamara Turk Wensveen 8 9,  Marina Babić 1 4,  Irit Gat-Viks 6,  Henrique Veiga-Fernandes 2,  Daniel Konrad 3,  Felix M Wensveen 1,  Bojan Polić 10
Affiliations

Affiliations

  • 1 Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
  • 2 Champalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal.
  • 3 Division of Pediatric Endocrinology and Diabetology and Children's Research Centre, University Children's Hospital, University of Zurich, Zurich, Switzerland.
  • 4 Innate Immunity, German Rheumatism Research Centre, Leibniz Institute, Berlin, Germany.
  • 5 Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
  • 6 School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
  • 7 Department of Infectious Diseases, Clinical Hospital Center Rijeka, Rijeka, Croatia.
  • 8 Center for Diabetes, Endocrinology and Cardiometabolism, Thallassotherapia, Opatija, Croatia.
  • 9 Department of Internal Medicine, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
  • 10 Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia. bojan.polic@uniri.hr.
  • # Contributed equally.
PMID: 38811816 DOI: 10.1038/s41590-024-01848-3
Abstract

Viral Infection makes us feel sick as the immune system alters systemic metabolism to better fight the pathogen. The extent of these changes is relative to the severity of disease. Whether blood glucose is subject to infection-induced modulation is mostly unknown. Here we show that strong, nonlethal Infection restricts systemic glucose availability, which promotes the Antiviral type I interferon (IFN-I) response. Following viral Infection, we find that IFNγ produced by γδ T cells stimulates pancreatic β cells to increase glucose-induced Insulin release. Subsequently, hyperinsulinemia lessens hepatic glucose output. Glucose restriction enhances IFN-I production by curtailing lactate-mediated inhibition of IRF3 and NF-κB signaling. Induced hyperglycemia constrained IFN-I production and increased mortality upon Infection. Our findings identify glucose restriction as a physiological mechanism to bring the body into a heightened state of responsiveness to viral pathogens. This immune-endocrine circuit is disrupted in hyperglycemia, possibly explaining why patients with diabetes are more susceptible to viral Infection.

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