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Microbiota regulates immune defense against respiratory tract influenza A virus infection
Iris K. Panga,1,
David R. Peaperc,
John H. Hoa,
Thomas S. Murrayc,d, and
aDepartment of Immunobiology, dDepartment of Pediatrics, and cLaboratory Medicine, Yale University School of Medicine, New Haven, CT 06520; and bDepartment of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan
Edited by Dan R. Littman, New York University Medical Center, New York, NY, and approved February 7, 2011 (received for review December 23, 2010)
Although commensal bacteria are crucial in maintaining immunehomeostasis of the intestine, the role of commensal bacteriain immune responses at other mucosal surfaces remains less clear.Here, we show that commensal microbiota composition criticallyregulates the generation of virus-specific CD4 and CD8 T cellsand antibody responses following respiratory influenza virusinfection. By using various antibiotic treatments, we foundthat neomycin-sensitive bacteria are associated with the inductionof productive immune responses in the lung. Local or distalinjection of Toll-like receptor (TLR) ligands could rescue theimmune impairment in the antibiotic-treated mice. Intact microbiotaprovided signals leading to the expression of mRNA for pro–IL-1βand pro–IL-18 at steady state. Following influenza virusinfection, inflammasome activation led to migration of dendriticcells (DCs) from the lung to the draining lymph node and T-cellpriming. Our results reveal the importance of commensal microbiotain regulating immunity in the respiratory mucosa through theproper activation of inflammasomes.
Author contributions: T.I., I.K.P., Y.K., D.R.P., T.S.M., andA.I. designed research; T.I., I.K.P., Y.K., D.R.P., J.H.H.,and T.S.M. performed research; T.I., I.K.P., Y.K., D.R.P., J.H.H.,T.S.M., and A.I. analyzed data; and T.I., I.K.P., D.R.P., T.S.M.,and A.I. wrote the paper.
1T.I. and I.K.P. contributed equally to this work.