Coordinated inflammatory responses dictate Marburg virus control by reservoir bats

Jonathan C. Guito, Shannon G. M. Kirejczyk, Amy J. Schuh, Brian R. Amman, Tara K. Sealy, James Graziano, Jessica R. Spengler, Jessica R. Harmon, David M. Wozniak, Joseph B. Prescott () and Jonathan S. Towner ()
Additional contact information
Jonathan C. Guito: Centers for Disease Control and Prevention
Shannon G. M. Kirejczyk: Centers for Disease Control and Prevention
Amy J. Schuh: Centers for Disease Control and Prevention
Brian R. Amman: Centers for Disease Control and Prevention
Tara K. Sealy: Centers for Disease Control and Prevention
James Graziano: Centers for Disease Control and Prevention
Jessica R. Spengler: Centers for Disease Control and Prevention
Jessica R. Harmon: Centers for Disease Control and Prevention
David M. Wozniak: Robert Koch Institute
Joseph B. Prescott: Centers for Disease Control and Prevention
Jonathan S. Towner: Centers for Disease Control and Prevention

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Bats are increasingly recognized as reservoirs of emerging zoonotic pathogens. Egyptian rousette bats (ERBs) are the known reservoir of Marburg virus (MARV), a filovirus that causes deadly Marburg virus disease (MVD) in humans. However, ERBs harbor MARV asymptomatically, likely due to a coadapted and specific host immunity-pathogen relationship. Recently, we measured transcriptional responses in MARV-infected ERB whole tissues, showing that these bats possess a disease tolerant strategy that limits pro-inflammatory gene induction, presumably averting MVD-linked immunopathology. However, the host resistant strategy by which ERBs actively limit MARV burden remains elusive, which we hypothesize requires localized inflammatory responses unresolvable at bulk-tissue scale. Here, we use dexamethasone to attenuate ERB pro-inflammatory responses and assess MARV replication, shedding and disease. We show that MARV-infected ERBs naturally mount coordinated pro-inflammatory responses at liver foci of infection, comprised of recruited mononuclear phagocytes and T cells, the latter of which proliferate with likely MARV-specificity. When pro-inflammatory responses are diminished, ERBs display heightened MARV replication, oral/rectal shedding and severe MVD-like liver pathology, demonstrating that ERBs balance immunoprotective tolerance with discreet MARV-resistant pro-inflammatory responses. These data further suggest that natural ERB immunomodulatory stressors like food scarcity and habitat disruption may potentiate viral shedding, transmission and therefore outbreak risk.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-46226-7 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:15:y:2024:i:1:d:10.1038_s41467-024-46226-7

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

DOI: 10.1038/s41467-024-46226-7

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 ().