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Commensal bacteria calibrate the activation threshold of innate antiviral immunity.

TitleCommensal bacteria calibrate the activation threshold of innate antiviral immunity.
Publication TypeJournal Article
Year of Publication2012
AuthorsAbt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T, Sonnenberg GF, Paley MA, Antenus M, Williams KL, Erikson J, E Wherry J, Artis D
JournalImmunity
Volume37
Issue1
Pagination158-70
Date Published2012 Jul 27
ISSN1097-4180
KeywordsAdaptive Immunity, Animals, Anti-Bacterial Agents, Arenaviridae Infections, Bacteria, Disease Susceptibility, Immunity, Innate, Interferons, Lymphocytic choriomeningitis virus, Macrophages, Mice, Mice, Inbred C57BL, Orthomyxoviridae, Orthomyxoviridae Infections, Viruses
Abstract

Signals from commensal bacteria can influence immune cell development and susceptibility to infectious or inflammatory diseases. However, the mechanisms by which commensal bacteria regulate protective immunity after exposure to systemic pathogens remain poorly understood. Here, we demonstrate that antibiotic-treated (ABX) mice exhibit impaired innate and adaptive antiviral immune responses and substantially delayed viral clearance after exposure to systemic LCMV or mucosal influenza virus. Furthermore, ABX mice exhibited severe bronchiole epithelial degeneration and increased host mortality after influenza virus infection. Genome-wide transcriptional profiling of macrophages isolated from ABX mice revealed decreased expression of genes associated with antiviral immunity. Moreover, macrophages from ABX mice exhibited defective responses to type I and type II IFNs and impaired capacity to limit viral replication. Collectively, these data indicate that commensal-derived signals provide tonic immune stimulation that establishes the activation threshold of the innate immune system required for optimal antiviral immunity.

DOI10.1016/j.immuni.2012.04.011
Alternate JournalImmunity
PubMed ID22705104
PubMed Central IDPMC3679670
Grant List2-P30 CA016520 / CA / NCI NIH HHS / United States
AI061570 / AI / NIAID NIH HHS / United States
AI071309 / AI / NIAID NIH HHS / United States
AI074878 / AI / NIAID NIH HHS / United States
AI077098 / AI / NIAID NIH HHS / United States
AI078897 / AI / NIAID NIH HHS / United States
AI083022 / AI / NIAID NIH HHS / United States
AI087990 / AI / NIAID NIH HHS / United States
AI091759 / AI / NIAID NIH HHS / United States
AI095466 / AI / NIAID NIH HHS / United States
AI095608 / AI / NIAID NIH HHS / United States
DK50306 / DK / NIDDK NIH HHS / United States
HHSN266200500030C / AI / NIAID NIH HHS / United States
K08 DK093784 / DK / NIDDK NIH HHS / United States
K08-DK093784 / DK / NIDDK NIH HHS / United States
R01 AI061570 / AI / NIAID NIH HHS / United States
R01 AI071309 / AI / NIAID NIH HHS / United States
R01 AI074878 / AI / NIAID NIH HHS / United States
R01 AI095466 / AI / NIAID NIH HHS / United States
R01 AI102942 / AI / NIAID NIH HHS / United States
R21 AI077098 / AI / NIAID NIH HHS / United States
R21 AI083480 / AI / NIAID NIH HHS / United States
R21 AI087990 / AI / NIAID NIH HHS / United States
T32 AI007532 / AI / NIAID NIH HHS / United States
T32-AI007324 / AI / NIAID NIH HHS / United States
T32-AI007532 / AI / NIAID NIH HHS / United States
T32-AI05528 / AI / NIAID NIH HHS / United States
T32-RR007063 / RR / NCRR NIH HHS / United States
U01 AI095608 / AI / NIAID NIH HHS / United States
U19 AI083022 / AI / NIAID NIH HHS / United States

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