Commensal bacteria calibrate the activation threshold of innate antiviral immunity.
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.
Department of Microbiology and Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Michael C
MC
Abt
Lisa C
LC
Osborne
Laurel A
LA
Monticelli
Travis A
TA
Doering
Theresa
T
Alenghat
Gregory F
GF
Sonnenberg
Michael A
MA
Paley
Marcelo
M
Antenus
Katie L
KL
Williams
Jan
J
Erikson
E John
EJ
Wherry
David
D
Artis
D056704:Adaptive Immunity; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001117:Arenaviridae Infections / Q000235:genetics / Q000276:immunology; D001419:Bacteria / Q000187:drug effects / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D007113:Immunity, Innate; D007372:Interferons / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology; D014780:Viruses / Q000276:immunology*
D000900:Anti-Bacterial Agents; D007372:Interferons