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In recent years gram-positive (G<jats:sup>+<\/jats:sup>) bacteria, most commonly staphylococci, are thought to be the main pathogens. Micheliolide (MCL) was demonstrated to provide a therapeutic role in rheumatoid arthritis, inflammatory intestinal disease, colitis-associated cancer, and lipopolysaccharide (LPS, the main component of G<jats:sup>\u2212<\/jats:sup>bacterial cell wall) induced septic shock. We proved here that MCL played an anti-inflammatory role in<jats:italic>Staphylococcus aureus (S. aureus<\/jats:italic>) and methicillin-resistant<jats:italic>S. aureus<\/jats:italic>(MRSA) induced peritonitis. It inhibited the expression of inflammatory cytokines and chemokines in macrophages and dendritic cells upon stimulation with peptidoglycan (PGN, the main cell wall composition of G<jats:sup>+<\/jats:sup>bacteria). PI3K\/Akt and NF-\u03baB pathways account for the anti-inflammatory role of MCL after PGN stimulation. MCL reduced IL-6 secretion through down-regulating NF-\u03baB activation and improved the survival status in mice challenged with a lethal dose of<jats:italic>S. aureus<\/jats:italic>. In MRSA infection mouse model, MCL down-regulated the expression of IL-6, TNF-\u03b1, MCP-1\/CCL2 and IFN-\u03b3 in sera, and ameliorated the organ damage of liver and kidney. In conclusion, MCL can help maintain immune equilibrium and decrease PGN,<jats:italic>S. aureus<\/jats:italic>and MRSA-triggered inflammatory response. These provide the rationality for the potential usage of MCL in sepsis caused by G<jats:sup>+<\/jats:sup>bacteria (e.g.,<jats:italic>S. aureus<\/jats:italic>) and antibiotic-resistant bacteria (e.g., MRSA).<\/jats:p>","DOI":"10.1038\/srep41964","type":"journal-article","created":{"date-parts":[[2017,2,6]],"date-time":"2017-02-06T10:51:04Z","timestamp":1486378264000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Micheliolide provides protection of mice against Staphylococcus aureus and MRSA infection by down-regulating inflammatory response"],"prefix":"10.1038","volume":"7","author":[{"given":"Xinru","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weigang","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel","family":"Benlahrech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhui","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuejuan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,6]]},"reference":[{"key":"BFsrep41964_CR1","first-page":"1","volume":"62","author":"MJ Hall","year":"2011","unstructured":"Hall, M. 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