Editors' ChoiceHost-Microbe Interactions

Why Not Take Antibiotics for the Flu?

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Science Signaling  05 Apr 2011:
Vol. 4, Issue 167, pp. ec94
DOI: 10.1126/scisignal.4167ec94

The role of commensal bacteria in maintaining immune homeostasis in the gut is well known; moreover, the specific composition of the gut microbiota may influence the development of various pathophysiological conditions. Wondering whether commensal bacteria affect immune responses at other sites, Ichinohe et al. verified that 4 weeks of treatment with a combination of antibiotics altered the composition of mouse commensal bacteria and determined the effect of this treatment on the response to intranasal infection with A/PR8 influenza virus. Both virion-specific antibody titers and T cell responses (interferon-γ production and number of cytotoxic T cells) were decreased in antibiotic-treated mice compared with untreated controls, and pulmonary viral titers were increased. Analyses of the effects of individual antibiotics implicated neomycin, which depleted Gram-positive gut (but not nasal) bacteria, in this suppression of the immune response. The adaptive immune response to respiratory infection with influenza depends on activation of inflammasomes [multiprotein complexes implicated in the caspase-1–dependent processing and secretion of proinflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18], and antibiotic treatment did not diminish immune responses that do not require the inflammasome. Either local (intranasal) or distant (intrarectal) inoculation with a Toll-like receptor agonist restored the response to influenza virus, whereas depletion of regulatory T cells did not. IL-1β secretion depends not only on inflammasome activation but also on a priming signal that stimulates its own transcription and that of the inflammasome component NLRP3. Antibiotic treatment decreased the abundance of the mRNAs encoding pro–IL-1β, pro–IL-18, and NLRP3 even before infection, as well as postinfection secretion of mature IL-1β, suggesting that commensal bacteria provide a constitutive priming signal. Antibiotics also inhibited migration of respiratory dendritic cells to lymph nodes to activate T cells, a defect also found in mice deficient in caspase-1. Thus, the authors propose that commensal bacteria provide a signal required for inflammasome-dependent immune responses to respiratory infection, which is lost with antibiotic-mediated disruption of the microbiota.

T. Ichinohe, I. K. Pang, Y. Kumamoto, D. R. Peaper, J. H. Ho, T. S. Murray, A. Iwasaki, Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl. Acad. Sci. U.S.A. 108, 5354–5359 (2011). [Abstract] [Full Text]

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