Coordinated inflammatory responses dictate Marburg virus control by reservoir bats.

Autor: Guito JC; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA., Kirejczyk SGM; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA.; Division of Pathology, Emory National Primate Research Center, Emory University, Atlanta, GA, 30329, USA.; StageBio, Mount Jackson, VA, 22842, USA., Schuh AJ; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA., Amman BR; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA., Sealy TK; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA., Graziano J; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA., Spengler JR; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA., Harmon JR; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA., Wozniak DM; Center for Biological Threats and Special Pathogens, Robert Koch Institute, 13353, Berlin, Germany.; Virology Department, Bernhard-Nocht-Institute for Tropical Medicine, 20359, Hamburg, Germany., Prescott JB; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA. prescottj@rki.de.; Center for Biological Threats and Special Pathogens, Robert Koch Institute, 13353, Berlin, Germany. prescottj@rki.de., Towner JS; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, 30329, USA. jit8@cdc.gov.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 28; Vol. 15 (1), pp. 1826. Date of Electronic Publication: 2024 Feb 28.
DOI: 10.1038/s41467-024-46226-7
Abstrakt: 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.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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