{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:42:28Z","timestamp":1793385748921,"version":"4.5.0"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Successful bacterial pathogens have evolved to avoid activating an innate immune system in the host that responds to the pathogen through distinct Toll-like receptors (TLRs). The general class of biochemical components that activate TLRs has been studied extensively, but less is known about how TLRs interact with the class of compounds that are still associated with the live pathogen. Accordingly, we examined the activation of surface assembled TLR 2, 4, and 5 with live Tier 1 Gram-negative pathogens that included\n                    <jats:italic>Yersinia pestis<\/jats:italic>\n                    (plague),\n                    <jats:italic>Burkholderia mallei<\/jats:italic>\n                    (glanders),\n                    <jats:italic>Burkholderia pseudomallei<\/jats:italic>\n                    (melioidosis), and\n                    <jats:italic>Francisella tularensis<\/jats:italic>\n                    (tularemia). We found that\n                    <jats:italic>Y. pestis<\/jats:italic>\n                    CO92 grown at 28\u00b0C activated TLR2 and TLR4, but at 37\u00b0C the pathogen activated primarily TLR2. Although\n                    <jats:italic>B. mallei<\/jats:italic>\n                    and\n                    <jats:italic>B. pseudomallei<\/jats:italic>\n                    are genetically related, the former microorganism activated predominately TLR4, while the latter activated predominately TLR2. The capsule of wild-type\n                    <jats:italic>B. pseudomallei<\/jats:italic>\n                    1026b was found to mitigate the activation of TLR2 and TLR4 when compared to a capsule mutant. Live\n                    <jats:italic>F. tularensis<\/jats:italic>\n                    (Ft) Schu S4 did not activate TLR2 or 4, although the less virulent Ft LVS and\n                    <jats:italic>F. novicida<\/jats:italic>\n                    activated only TLR2.\n                    <jats:italic>B. pseudomallei<\/jats:italic>\n                    purified flagellin or flagella attached to the microorganism activated TLR5. Activation of TLR5 was abolished by an antibody to TLR5, or a mutation of\n                    <jats:italic>fli<\/jats:italic>\n                    C, or elimination of the pathogen by filtration. In conclusion, we have uncovered new properties of the Gram-negative pathogens, and their interaction with TLRs of the host. Further studies are needed to include other microorganism to extend our observations with their interaction with TLRs, and to the possibility of leading to new efforts in therapeutics against these pathogens.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2021.745325","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T09:09:14Z","timestamp":1638263354000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella"],"prefix":"10.3389","volume":"11","author":[{"given":"Kei","family":"Amemiya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Dankmeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Bernhards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Fetterer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Waag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia L.","family":"Worsham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"DeShazer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen Recognition and Innate Immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.micpath.2015.07.004","article-title":"Comparison of the Early Host Immune Response to Two Widely Diverse Virulent Strains of Burkholderia Pseudomallei That Cause Acute or Chronic Infections in BALB\/c Mice","volume":"86","author":"Amemiya","year":"2015","journal-title":"Microbial Path."},{"key":"B3","doi-asserted-by":"publisher","first-page":"9247","DOI":"10.1073\/pnas.0502040102","article-title":"Evasion of Toll-Like Receptor 5 by Flagellated Bacteria","volume":"102","author":"Andersen-Nissen","year":"2005","journal-title":"Proc. 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