Commensal Bacteria Calibrate the Activation Threshold of Innate Antiviral Immunity

Department of Microbiology and Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Immunity (Impact Factor: 21.56). 06/2012; 37(1):158-70. DOI: 10.1016/j.immuni.2012.04.011
Source: PubMed


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.

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Available from: Travis Doering, Sep 18, 2015
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    • "Similarly, in the lung, it is increasingly understood that that innate signaling is important in the generation of respiratory B cell responses. Although the respiratory microbiome is more limited than that of the gut, it nevertheless contributes bacterial components that enhance and modulate both innate and adaptive immune responses (Abt et al. 2012). Furthermore, following B cell receptor engagement, pattern recognition receptors including TLR9 and TLR10 are up-regulated on human B cells, providing additional signals that increase immunoglobulin production and are the likely basis for adjuvant effects (Bernasconi et al. 2003). "
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    • "The most dramatic event that occurs at birth is certainly the initial colonization of the gastrointestinal tract by the microbiota. Strikingly, macrophages isolated from mice treated with antibiotics show reduced expression of IFN-responsive genes, suggesting that signals derived from commensal bacteria influence systemic innate antiviral responses (115). Furthermore, this might implicate tunable chromatin level changes as DCs from germ-free or antibiotic-treated mice show reduced H3K4me3 deposits at specific inflammatory genes (116). "
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    • "Further investigation by Abt et al. indicated that antibiotic-treated mice more readily succumbed to influenza infection when compared to conventional counterparts (108). T cell responses in antibiotic-treated mice indicated a decrease in CD8 virus-specific T cells, further confirming that commensal microbiota modulates T cell responses to systemic viral infection (108). The authors concluded that the higher susceptibility of antibiotic-treated mice to infection was due to an inability of macrophages to respond to type-1 interferon and limit viral replication. "
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