{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:30:35Z","timestamp":1790281835798,"version":"4.1.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Infectious pneumonias exact an unacceptable mortality burden worldwide. Efforts to protect populations from pneumonia have focused historically on antibiotic development and vaccine-enhanced adaptive immunity. However, we have reported recently that the lungs\u2019 innate defenses can be induced therapeutically by inhalation of a bacterial lysate that protects mice against otherwise lethal pneumonia. In this study, we tested in mice the hypothesis that TLRs are required for this antimicrobial phenomenon and found that resistance could not be induced in the absence of the TLR signaling adaptor protein MyD88. We then attempted to recapitulate the protection afforded by the bacterial lysate by stimulating the lung epithelium with aerosolized synthetic TLR ligands. Although most single or combination treatments yielded no protection, simultaneous treatment with ligands for TLR2\/6 and TLR9 conferred robust, synergistic protection against virulent Gram-positive and Gram-negative pathogens. Protection was associated with rapid pathogen killing in the lungs, and pathogen killing could be induced from lung epithelial cells in isolation. Taken together, these data demonstrate the requirement for TLRs in inducible resistance against pneumonia, reveal a remarkable, unanticipated synergistic interaction of TLR2\/6 and TLR9, reinforce the emerging evidence supporting the antimicrobial capacity of the lung epithelium, and may provide the basis for a novel clinical therapeutic that can protect patients against pneumonia during periods of peak vulnerability.<\/jats:p>","DOI":"10.4049\/jimmunol.1002122","type":"journal-article","created":{"date-parts":[[2011,4,12]],"date-time":"2011-04-12T01:44:58Z","timestamp":1302572698000},"page":"5916-5926","source":"Crossref","is-referenced-by-count":108,"title":["Synergistic Interactions of TLR2\/6 and TLR9 Induce a High Level of Resistance to Lung Infection in Mice"],"prefix":"10.1093","volume":"186","author":[{"given":"Jeffrey M","family":"Duggan","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dahui","family":"You","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey O","family":"Cleaver","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek T","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Joshua","family":"Garza","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco A","family":"Guzm\u00e1n Pruneda","sequence":"additional","affiliation":[{"name":"Tecnol\u00f3gico de Monterrey Escuela de Medicina , Monterrey, Nuevo Le\u00f3n ,","place":["Mexico 64710"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Tuvim","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX 77030"},{"name":"Center for Infectious and Inflammatory Disease, Institute of Biosciences and Technology, Texas A&M Health Science Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiexin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burton F","family":"Dickey","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX 77030"},{"name":"Center for Infectious and Inflammatory Disease, Institute of Biosciences and Technology, Texas A&M Health Science Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott E","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center , Houston, TX 77030"},{"name":"Center for Infectious and Inflammatory Disease, Institute of Biosciences and Technology, Texas A&M Health Science Center , Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,5,15]]},"reference":[{"key":"2025032411253147400_r1","doi-asserted-by":"crossref","first-page":"e76","DOI":"10.1371\/journal.pmed.0030076","article-title":"Lung infection\u2014a public health priority","volume":"3","author":"Mizgerd","year":"2006","journal-title":"PLoS Med."},{"key":"2025032411253147400_r2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/nature02759","article-title":"The challenge of emerging and re-emerging infectious diseases","volume":"430","author":"Morens","year":"2004","journal-title":"Nature"},{"key":"2025032411253147400_r3","volume-title":"The World Health Report 2004\u2014Changing History.","author":"WHO","year":"2004"},{"key":"2025032411253147400_r4","first-page":"895","article-title":"Global estimate of the incidence of clinical pneumonia among children under five years of age","volume":"82","author":"Rudan","year":"2004","journal-title":"Bull. 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