{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:13:44Z","timestamp":1791000824332,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T00:00:00Z","timestamp":1447718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. National Institutes of Health","doi-asserted-by":"crossref","award":["R01 AI116453"],"award-info":[{"award-number":["R01 AI116453"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Brucella abortus is a Gram-negative intracellular bacterial pathogen that causes a zoonosis of worldwide occurrence, leading to undulant fever in humans and abortion in domestic animals. B. abortus is recognized by several pattern-recognition receptors triggering pathways during the host innate immune response. Therefore, here, we determined the cooperative role of TLR9 with TLR2 or TLR6 receptors in sensing Brucella. Furthermore, we deciphered the host innate immune response against B. abortus or its DNA, emphasizing the role of TLR9-MAPK\/NF-\u03baB signaling pathways in the production of proinflammatory cytokines. TLR9 is required for the initial host control of B. abortus, but this TLR was dispensable after 6 wk of infection. The susceptibility of TLR9\u2212\/\u2212-infected animals to Brucella paralleled with lower levels of IFN-\u03b3 produced by mouse splenocytes stimulated with this pathogen compared with wild-type cells. However, no apparent cooperative interplay was observed between TLR2\u2013TLR9 or TLR6\u2013TLR9 receptors to control infection. Moreover, B. abortus or its DNA induced activation of MAPK\/NF-\u03baB pathways and production of IL-12 and TNF-\u03b1 by macrophages partially dependent on TLR9 but completely dependent on MyD88. In addition, B. abortus-derived CpG oligonucleotides required TLR9 to promote IL-12 and TNF-\u03b1 production by macrophages. By confocal microscopy, we demonstrated that TLR9 redistributed and colocalized with lysosomal-associated membrane protein-1 upon Brucella infection. Thus, B. abortus induced TLR9 traffic, leading to cell signaling activation and IL-12 and TNF-\u03b1 production. Although TLR9 recognized Brucella CpG motifs, our results suggest a new pathway of B. abortus DNA-activating macrophages independent of TLR9.<\/jats:p>","DOI":"10.1189\/jlb.4a0815-346r","type":"journal-article","created":{"date-parts":[[2015,11,18]],"date-time":"2015-11-18T03:19:18Z","timestamp":1447816758000},"page":"771-780","source":"Crossref","is-referenced-by-count":49,"title":["TLR9 is required for MAPK\/NF-\u03baB activation but does not cooperate with TLR2 or TLR6 to induce host resistance to <i>Brucella abortus<\/i>"],"prefix":"10.1093","volume":"99","author":[{"given":"Marco T\u00falio","family":"Gomes","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila Carneiro","family":"Campos","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme de Sousa","family":"Pereira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella Castanheira","family":"Bartholomeu","sequence":"additional","affiliation":[{"name":"Departamento de Parasitologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Splitter","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin-Madison School of Veterinary Medicine , Madison, Wisconsin , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio Costa","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,11,17]]},"reference":[{"key":"2023013012482796700_B1","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1128\/CMR.00046-08","article-title":"Pathogen recognition and inflammatory signaling in innate immune defenses","volume":"22","author":"Mogensen","year":"2009","journal-title":"Clin. 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Immunol."},{"key":"2023013012482796700_B7","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/ni1112","article-title":"Toll-like receptor control of the adaptive immune responses","volume":"5","author":"Iwasaki","year":"2004","journal-title":"Nat. Immunol."},{"key":"2023013012482796700_B8","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1084\/jem.20051782","article-title":"TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis","volume":"202","author":"Bafica","year":"2005","journal-title":"J. Exp. Med."},{"key":"2023013012482796700_B9","doi-asserted-by":"crossref","first-page":"5916","DOI":"10.4049\/jimmunol.1002122","article-title":"Synergistic interactions of TLR2\/6 and TLR9 induce a high level of resistance to lung infection in mice","volume":"186","author":"Duggan","year":"2011","journal-title":"J. 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