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Immunity. 2012 Jul 27;37(1):158-70. doi: 10.1016/j.immuni.2012.04.011. Epub 2012 Jun 14.

Commensal bacteria calibrate the activation threshold of innate antiviral immunity.

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  • 1Department of Microbiology and Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

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PMID:
22705104
[PubMed - indexed for MEDLINE]
PMCID:
PMC3679670
Free PMC Article

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