{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T23:35:23Z","timestamp":1772753723367,"version":"3.50.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The lipopolysaccharides (LPSs) of<jats:italic>Rhodobacter<\/jats:italic>are reported to be TLR4 antagonists. Accordingly, the extract of<jats:italic>Rhodobacter azotoformans<\/jats:italic>(RAP99) is used as a health supplement for humans and animals in Japan to regulate immune responses<jats:italic>in vivo<\/jats:italic>. We previously analyzed the LPS structure of RAP99 (RAP99-LPS) and found it is different from that of<jats:italic>E. coli<\/jats:italic>-LPS but similar to lipid A from<jats:italic>Rhodobacter sphaeroides<\/jats:italic>(RSLA), a known antagonist of TLR4, with both having three C14 fatty acyl groups, two C10 fatty acyl groups, and two phosphates. Here we show that RAP99-LPS has an immune stimulatory activity and acts as a TLR4 agonist. Pretreatment of RAP99-LPS suppressed<jats:italic>E. coli<\/jats:italic>-LPS-mediated weight loss, suggesting it is an antagonist against<jats:italic>E. coli<\/jats:italic>-LPS like other LPS isolated from<jats:italic>Rhodobacter<\/jats:italic>. However, injections of RAP99-LPS caused splenomegaly and increased immune cell numbers in C57BL\/6 mice but not in C3H\/HeJ mice, suggesting that RAP99-LPS stimulates immune cells<jats:italic>via<\/jats:italic>TLR4. Consistently, RAP99-LPS suppressed the lung metastasis of B16F1 tumor cells and enhanced the expression of TLR3-mediated chemokines. These results suggest that RAP99-LPS is a TLR4 agonist that enhances the activation status of the immune system to promote anti-viral and anti-tumor activity<jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fimmu.2021.675909","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T05:23:36Z","timestamp":1621920216000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Rhodobacter azotoformans LPS (RAP99-LPS) Is a TLR4 Agonist That Inhibits Lung Metastasis and Enhances TLR3-Mediated Chemokine 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