{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T18:23:09Z","timestamp":1789928589574,"version":"4.0.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"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":[[2012,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The innate immune system has developed to acquire a wide variety of pattern-recognition receptors (PRRs) to identify potential pathogens, whereas pathogens have also developed to escape host innate immune responses. ITIM-bearing receptors are attractive targets for pathogens to attenuate immune responses against them; however, the in vivo role of the inhibitory PRRs in host\u2013bacteria interactions remains unknown. We demonstrate in this article that Staphylococcus aureus, a major Gram-positive bacteria, exploits inhibitory PRR paired Ig-like receptor (PIR)-B on macrophages to suppress ERK1\/2 and inflammasome activation, and subsequent IL-6 and IL-1\u03b2 secretion. Consequently, Pirb\u2212\/\u2212 mice infected with S. aureus showed enhanced inflammation and more effective bacterial clearance, resulting in resistance to the sepsis. Screening of S. aureus mutants identified lipoteichoic acid (LTA) as an essential bacterial cell wall component required for binding to PIR-B and modulating inflammatory responses. In vivo, however, an LTA-deficient S. aureus mutant was highly virulent and poorly recognized by macrophages in both wild-type and Pirb\u2212\/\u2212 mice, demonstrating that LTA recognition by PRRs other than PIR-B mediates effective bacterial elimination. These results provide direct evidence that bacteria exploit the inhibitory receptor for virulence, and host immune system counterbalances the infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1201940","type":"journal-article","created":{"date-parts":[[2012,11,14]],"date-time":"2012-11-14T22:16:08Z","timestamp":1352931368000},"page":"5903-5911","source":"Crossref","is-referenced-by-count":45,"title":["Inhibitory Receptor Paired Ig-like Receptor B Is Exploited by\n                    <i>Staphylococcus aureus<\/i>\n                    for Virulence"],"prefix":"10.1093","volume":"189","author":[{"given":"Masafumi","family":"Nakayama","sequence":"first","affiliation":[{"name":"Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kurokawa","sequence":"additional","affiliation":[{"name":"The National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University , Busan 609-735,","place":["Korea"]},{"name":"Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo , Tokyo 113-0033,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyohei","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575,","place":["Japan"]},{"name":"Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine , Sendai 980-8574,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bok Luel","family":"Lee","sequence":"additional","affiliation":[{"name":"The National Research Laboratory of Defense Proteins, College of Pharmacy, Pusan National University , Busan 609-735,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhisa","family":"Sekimizu","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo , Tokyo 113-0033,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Kubagawa","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham , Birmingham, AL 35294"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Hiramatsu","sequence":"additional","affiliation":[{"name":"Department of Bacteriology, Juntendo University School of Medicine , Tokyo 113-8421,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Yagita","sequence":"additional","affiliation":[{"name":"Department of Immunology, Juntendo University School of Medicine , Tokyo 113-8421,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of Immunology, Juntendo University School of Medicine , Tokyo 113-8421,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Takai","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Underhill","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center , Los Angeles, CA 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Aderem","sequence":"additional","affiliation":[{"name":"Seattle Biomedical Research Institute , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kouetsu","family":"Ogasawara","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Institute of Development, Aging and Cancer, Tohoku University , Sendai 980-8575,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,12,15]]},"reference":[{"key":"2025032409405039700_r1","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1056\/NEJMoa022139","article-title":"The epidemiology of sepsis in the United States from 1979 through 2000","volume":"348","author":"Martin","year":"2003","journal-title":"N. 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