Metabolic deficiencies underlie reduced plasmacytoid dendritic cell IFN-I production following viral infection

Trever T. Greene, Yeara Jo, Carolina Chiale, Monica Macal, Ziyan Fang, Fawziyah S. Khatri, Alicia L. Codrington, Katelynn R. Kazane, Elizabeth Akbulut, Shobha Swaminathan, Yu Fujita, Patricia Fitzgerald-Bocarsly, Thekla Cordes, Christian Metallo, David A. Scott and Elina I. Zúñiga ()
Additional contact information
Trever T. Greene: University of California, San Diego
Yeara Jo: University of California, San Diego
Carolina Chiale: University of California, San Diego
Monica Macal: University of California, San Diego
Ziyan Fang: University of California, San Diego
Fawziyah S. Khatri: University of California, San Diego
Alicia L. Codrington: Rutgers New Jersey Medical School
Katelynn R. Kazane: University of California, San Diego
Elizabeth Akbulut: Rutgers New Jersey Medical School
Shobha Swaminathan: The State University of New Jersey, Rutgers, New Jersey Medical School
Yu Fujita: The Jikei University School of Medicine
Patricia Fitzgerald-Bocarsly: Rutgers New Jersey Medical School
Thekla Cordes: Technische Universität Braunschweig
Christian Metallo: Salk Institute for Biological Sciences
David A. Scott: Sanford Burnham Prebys Medical Discovery Institute
Elina I. Zúñiga: University of California, San Diego

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Type I Interferons (IFN-I) are central to host protection against viral infections, with plasmacytoid dendritic cells (pDC) being the most significant source, yet pDCs lose their IFN-I production capacity following an initial burst of IFN-I, resulting in susceptibility to secondary infections. The underlying mechanisms of these dynamics are not well understood. Here we find that viral infection reduces the capacity of pDCs to engage both oxidative and glycolytic metabolism. Mechanistically, we identify lactate dehydrogenase B (LDHB) as a positive regulator of pDC IFN-I production in mice and humans; meanwhile, LDHB deficiency is associated with suppressed IFN-I production, pDC metabolic capacity, and viral control following infection. In addition, preservation of LDHB expression is sufficient to partially retain the function of otherwise exhausted pDCs, both in vitro and in vivo. Furthermore, restoring LDHB in vivo in pDCs from infected mice increases IFNAR-dependent, infection-associated pathology. Our work thus identifies a mechanism for balancing immunity and pathology during viral infections, while also providing insight into the highly preserved infection-driven pDC inhibition.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-56603-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56603-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-56603-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().