{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:20:47Z","timestamp":1791584447556,"version":"4.3.4"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"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:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Streptococcus pneumoniae<\/jats:italic> is one of the main causes of community-acquired infections in the lung alveoli in children and the elderly. Alveolar macrophages (AM) patrol alveoli in homeostasis and under infectious conditions. However, the molecular adaptations of AM upon infections with <jats:italic>Streptococcus pneumoniae<\/jats:italic> are incompletely resolved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used a comparative transcriptomic and proteomic approach to provide novel insights into the cellular mechanism that changes the molecular signature of AM during lung infections. Using a tandem mass spectrometry approach to murine cell-sorted AM, we revealed significant proteomic changes upon lung infection with <jats:italic>Streptococcus pneumoniae.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AM showed a strong neutrophil-associated proteomic signature, such as expression of CD11b, MPO, neutrophil gelatinases, and elastases, which was associated with phagocytosis of recruited neutrophils. Transcriptomic analysis indicated intrinsic expression of CD11b by AM. Moreover, comparative transcriptomic and proteomic profiling identified CD11b as the central molecular hub in AM, which influenced neutrophil recruitment, activation, and migration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In conclusion, our study provides novel insights into the intrinsic molecular adaptations of AM upon lung infection with <jats:italic>Streptococcus pneumoniae<\/jats:italic> and reveals profound alterations critical for effective antimicrobial immunity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1227191","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T07:09:07Z","timestamp":1695107347000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Comparative transcriptomic and proteomic signature of lung alveolar macrophages reveals the integrin CD11b as a regulatory hub during pneumococcal pneumonia infection"],"prefix":"10.3389","volume":"14","author":[{"given":"Kristina","family":"Zec","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Thiebes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Bottek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devon","family":"Siemes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa","family":"Spangenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duc Viet","family":"Trieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Kirstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirojah","family":"Subramaniam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Christ","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Jendrossek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Loose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Wagenlehner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jadwiga","family":"Jablonska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"Bracht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Sitek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Budeus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludger","family":"Klein-Hitpass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Theegarten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Shevchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Engel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(04)00938-7","article-title":"Streptococcus pneumoniae colonisation: the key to pneumococcal disease","volume":"4","author":"Bogaert","year":"2004","journal-title":"Lancet Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.53.3.159","article-title":"Pneumococcal serotypes and their clinical relevance","volume":"53","author":"Kalin","year":"1998","journal-title":"Thorax"},{"key":"B3","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1038\/nri3600","article-title":"Alveolar macrophages: plasticity in a tissue-specific context","volume":"14","author":"Hussell","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80545-0","article-title":"The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis","volume":"96","author":"Munger","year":"1999","journal-title":"Cell"},{"key":"B5","article-title":"Cytokine modulation of the immunosuppressive phenotype of pulmonary alveolar macrophage populations","volume":"86","author":"Bilyk","year":"1995","journal-title":"Immunology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.2613","article-title":"Inhibition of IL-10 receptor function in alveolar macrophages by Toll-like receptor agonists","volume":"172","author":"Fernandez","year":"2004","journal-title":"J Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.94.07091678","article-title":"Pulmonary macrophages","volume":"7","author":"Lohmann-Matthes","year":"1994","journal-title":"Eur Respir J"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.10.5380","article-title":"Alveolar macrophage apoptosis contributes to pneumococcal clearance in a resolving model of pulmonary infection","volume":"171","author":"Dockrell","year":"2003","journal-title":"J Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2010-0210OC","article-title":"Earliest innate immune responses require macrophage RelA during pneumococcal pneumonia","volume":"45","author":"Pittet","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200207-698OC","article-title":"Alveolar macrophages have a protective antiinflammatory role during murine pneumococcal pneumonia","volume":"167","author":"Knapp","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.84","article-title":"CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs","volume":"9","author":"Duan","year":"2016","journal-title":"Mucosal Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1086\/498874","article-title":"CD11b regulates recruitment of alveolar macrophages but not pulmonary dendritic cells after pneumococcal challenge","volume":"193","author":"Kirby","year":"2006","journal-title":"J Infect Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1086\/429633","article-title":"CD11b limits bacterial outgrowth and dissemination during murine pneumococcal pneumonia","volume":"191","author":"Rijneveld","year":"2005","journal-title":"J Infect Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002949","article-title":"Proteomic and bioinformatic profiling of neutrophils in CLL reveals functional defects that predispose to bacterial infections","volume":"5","author":"Subramaniam","year":"2021","journal-title":"Blood Adv"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.133042","article-title":"Pneumonia recovery reprograms the alveolar macrophage pool","volume":"5","author":"Guillon","year":"2020","journal-title":"JCI Insight"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy078","article-title":"Roles for endothelial cell and macrophage Gch1 and tetrahydrobiopterin in atherosclerosis progression","volume":"114","author":"Douglas","year":"2018","journal-title":"Cardiovasc Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0142979","article-title":"IL4I1 is a novel regulator of M2 macrophage polarization that can inhibit T cell activation via L-tryptophan and arginine depletion and IL-10 production","volume":"10","author":"Yue","year":"2015","journal-title":"PloS One"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00204","article-title":"How mouse macrophages sense what is going on","volume":"7","author":"Ley","year":"2016","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/s12964-019-0420-9","article-title":"Immature O-glycans recognized by the macrophage glycoreceptor CLEC10A (MGL) are induced by 4-hydroxy-tamoxifen, oxidative stress and DNA-damage in breast cancer cells","volume":"17","author":"Kurze","year":"2019","journal-title":"Cell Commun Signal"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2009.07.010","article-title":"The Dectin-2 family of C-type lectins in immunity and homeostasis","volume":"48","author":"Graham","year":"2009","journal-title":"Cytokine"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.05.017","article-title":"C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection","volume":"39","author":"Zhu","year":"2013","journal-title":"Immunity"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20162152","article-title":"Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span","volume":"214","author":"Misharin","year":"2017","journal-title":"J Exp Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1038\/s41467-023-37199-0","article-title":"Testicular macrophages are recruited during a narrow fetal time window and promote organ-specific developmental functions","volume":"14","author":"Gu","year":"2023","journal-title":"Nat Commun"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.617879","article-title":"Tissue-resident macrophage development and function","volume":"8","author":"Wu","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00070-4","article-title":"Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12","volume":"13","author":"Oppmann","year":"2000","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.3390\/cells9092044","article-title":"Decoding IL-23 signaling cascade for new therapeutic opportunities","volume":"9","author":"Pastor-Fernandez","year":"2020","journal-title":"Cells"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.39","article-title":"Characterization and biological significance of IL-23-induced neutrophil polarization","volume":"15","author":"Li","year":"2018","journal-title":"Cell Mol Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600138","article-title":"IL-17 promotes neutrophil-mediated immunity by activating microvascular pericytes and not endothelium","volume":"197","author":"Liu","year":"2016","journal-title":"J Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00535-12","article-title":"Pilus adhesin RrgA interacts with complement receptor 3, thereby affecting macrophage function and systemic pneumococcal disease","volume":"4","author":"Orrskog","year":"2012","journal-title":"mBio"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200424850","article-title":"Critical role for complement receptor 3 (CD11b\/CD18), but not for Fc receptors, in killing of Streptococcus pyogenes by neutrophils in human immune serum","volume":"35","author":"Nilsson","year":"2005","journal-title":"Eur J Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040731","article-title":"The scavenger receptor MARCO is required for lung defense against pneumococcal pneumonia and inhaled particles","volume":"200","author":"Arredouani","year":"2004","journal-title":"J Exp Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2011.01746.x","article-title":"Recognition of Streptococcus pneumoniae by the innate immune system","volume":"14","author":"Koppe","year":"2012","journal-title":"Cell Microbiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1004143","article-title":"Streptococcus pneumoniae stimulates a STING- and IFN regulatory factor 3-dependent type I IFN production in macrophages, which regulates RANTES production in macrophages, cocultured alveolar epithelial cells, and mouse lungs","volume":"188","author":"Koppe","year":"2012","journal-title":"J Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00394","article-title":"Cross talk between inhibitory immunoreceptor tyrosine-based activation motif-signaling and toll-like receptor pathways in macrophages and dendritic cells","volume":"8","author":"Hirsch","year":"2017","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1908","article-title":"Integrin CD11b negatively regulates TLR-triggered inflammatory responses by activating Syk and promoting degradation of MyD88 and TRIF","volume":"11","author":"Han","year":"2010","journal-title":"Cbl-b Nat Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1227191\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T07:09:12Z","timestamp":1695107352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1227191\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,18]]},"references-count":36,"alternative-id":["10.3389\/fimmu.2023.1227191"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1227191","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,18]]},"article-number":"1227191"}}