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Immunol."],"abstract":"<jats:p><jats:italic>Staphylococcus aureus<\/jats:italic> is a highly successful pathogen infecting various body parts and forming biofilms on natural and artificial surfaces resulting in difficult-to-treat and chronic infections. We investigated the secreted cytokines and proteomes of isolated peripheral blood mononuclear cells (PBMCs) from healthy volunteers exposed to methicillin-resistant <jats:italic>S. aureus<\/jats:italic> (MRSA) biofilms or planktonic bacteria. Additionally, the cytokine profiles in sera from patients with community-acquired pneumonia (CAP) caused by <jats:italic>S. aureus<\/jats:italic> were investigated. The aim was to gain insights into the immune response involved and differentiate between the planktonic and sessile MRSA forms. We identified 321 and 298 targets that were significantly differently expressed in PBMCs when exposed to planktonic or biofilm-embedded bacteria, respectively. PBMCs exposed to planktonic MRSA cells secreted increased levels of TNF-\u03b1, while IL-18 was elevated when exposed to the biofilm. The machine-learning analyses of the cytokine profiles obtained for the <jats:italic>in vitro<\/jats:italic> PBMCs and CAP sera distinguished between the two types of bacteria forms based on cytokines IL-18, IL12, and IL-17, and with a lower importance IL-6. Particularly, IL-18 which has not been correlated with <jats:italic>S. aureus<\/jats:italic> biofilms so far might represent a suitable marker for monitoring chronification during MRSA infection to individualize the therapy, but this hypothesis must be proved in clinical trials.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1334616","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T14:42:00Z","timestamp":1710945720000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring secretory proteome and cytokine kinetic of human peripheral blood mononuclear cells exposed to methicillin-resistant Staphylococcus aureus biofilms and planktonic bacteria"],"prefix":"10.3389","volume":"15","author":[{"given":"Reza","family":"Gheitasi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"R\u00f6ll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario M.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohadeseh","family":"Naseri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"K\u00f6nig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hortense","family":"Slevogt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias W.","family":"Pletz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliwia","family":"Makarewicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.13833","article-title":"Into the storm: Chasing the opportunistic pathogen Staphylococcus aureus from skin colonisation to life-threatening infections","volume":"19","author":"O'Gara","year":"2017","journal-title":"Environ Microbiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.cmrp.2018.01.001","article-title":"Methicillin-resistant Staphylococcus aureus: An update on the epidemiology, treatment options and infection control","volume":"8","author":"Boswihi","year":"2018","journal-title":"Curr Med Res Pract"},{"key":"B3","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s12178-018-9501-4","article-title":"Staphylococcus aureus evasion of host immunity in the setting of prosthetic joint infection: biofilm and beyond","volume":"11","author":"Ricciardi","year":"2018","journal-title":"Curr Rev Musculoskelet Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"fty023","DOI":"10.1093\/femspd\/fty023","article-title":"Chronic biofilm-based infections: skewing of the immune response","volume":"76","author":"Gonzalez","year":"2018","journal-title":"Pathog Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/nrmicro821","article-title":"Bacterial biofilms: from the natural environment to infectious diseases","volume":"2","author":"Hall-Stoodley","year":"2004","journal-title":"Nat Rev Microbiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.05.031","article-title":"Biofilm formation in Staphylococcus implant infections. 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