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Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Osteomyelitis (OMS) is a bone infection causing bone pain and severe complications. A balanced immune response is critical to eradicate infection without harming the host, yet pathogens manipulate immunity to establish a chronic infection. Understanding OMS-driven inflammation is essential for disease management, but comprehensive data on immune profiles and immune cell activation during OMS are lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using high-dimensional flow cytometry, we investigated the detailed innate and adaptive systemic immune cell populations in OMS and age- and sex-matched controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study revealed that OMS is associated with increased levels of immune regulatory cells, namely T regulatory cells, B regulatory cells, and T follicular regulatory cells. In addition, the expression of immune activation markers HLA-DR and CD86 was decreased in OMS, while the expression of immune exhaustion markers TIM-3, PD-1, PD-L1, and VISTA was increased. Members of the T follicular helper (Tfh) cell family as well as classical and typical memory B cells were significantly increased in OMS individuals. We also found a strong correlation between memory B cells and Tfh cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We conclude that OMS skews the host immune system towards the immunomodulatory arm and that the Tfh memory B cell axis is evident in OMS. Therefore, immune-directed therapies may be a promising alternative for eradication and recurrence of infection in OMS, particularly in individuals and areas where antibiotic resistance is a major concern.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1396592","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T04:31:11Z","timestamp":1714105871000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Osteomyelitis is associated with increased anti-inflammatory response and immune exhaustion"],"prefix":"10.3389","volume":"15","author":[{"given":"Jayagopi","family":"Surendar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roslind K.","family":"Hackenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Schmitt-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Ossendorff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Welle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Stoffel-Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Sage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Burger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter C.","family":"Wirtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas C.","family":"Strauss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A.","family":"Schildberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.89B5.19170","article-title":"A history of osteomyelitis from the Journal of Bone and Joint Surgery: 1948 TO 2006","volume":"89","author":"Klenerman","year":"2007","journal-title":"J Bone Joint Surg Br"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.N.01350","article-title":"Trends in the epidemiology of osteomyelitis: a population-based study, 1969 to 2009","volume":"97","author":"Kremers","year":"2015","journal-title":"J Bone Joint Surg Am"},{"key":"B3","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s12879-021-06274-6","article-title":"What is the burden of osteomyelitis in Germany? 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