Coordinated inflammatory responses dictate Marburg virus control by reservoir bats

作者：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 Prescott, Jonathan S. Towner · 发表于：Nature Communications · 年份：2024 · DOI：10.1038/s41467-024-46226-7 · 被引用次数：33 · 研究领域：Viral Infections and Outbreaks Research、Viral Infections and Vectors、COVID-19 epidemiological studies

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 habita...