Title | Commensal bacteria calibrate the activation threshold of innate antiviral immunity. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T, Sonnenberg GF, Paley MA, Antenus M, Williams KL, Erikson J, E Wherry J, Artis D |
Journal | Immunity |
Volume | 37 |
Issue | 1 |
Pagination | 158-70 |
Date Published | 2012 Jul 27 |
ISSN | 1097-4180 |
Keywords | Adaptive 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. |
DOI | 10.1016/j.immuni.2012.04.011 |
Alternate Journal | Immunity |
PubMed ID | 22705104 |
PubMed Central ID | PMC3679670 |
Grant List | 2-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 |
Submitted by alp2017 on May 20, 2015 - 10:32am