{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T07:17:13Z","timestamp":1775978233909,"version":"3.50.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"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:p><jats:italic>Legionella pneumophila<\/jats:italic>, an intracellular bacterium, may cause life-threatening pneumonia in immunocompromised individuals. Mononuclear cells and antibodies have been reported to be associated with the host defense response against<jats:italic>L. pneumophila.<\/jats:italic>This study is to determine whether<jats:italic>Legionella<\/jats:italic>peptidoglycan-associated lipoprotein (PAL)-specific CD8<jats:sup>+<\/jats:sup>T cells are directly associated with protection against<jats:italic>L. pneumophila<\/jats:italic>, with a focus on potential epitopes. Synthetic peptides derived from PAL of<jats:italic>L. pneumophila<\/jats:italic>were obtained and tested through in<jats:italic>vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>cytotoxic T lymphocyte (CTL) assays for immunogenicity. PAL DNA vaccines or a peptide epitope with or without CpG-oligodeoxynucleotides (ODN) was evaluated for protection against<jats:italic>L. pneumophila<\/jats:italic>infection in animal models. When mice were immunized with DNA vaccines expressing the PAL of<jats:italic>L. pneumophila<\/jats:italic>, they were significantly protected against a lethal challenge with<jats:italic>L. pneumophila<\/jats:italic>through induction of antigen-specific CD8<jats:sup>+<\/jats:sup>CTLs. Of the 13 PAL peptides tested, PAL<jats:sub>92-100<\/jats:sub>(EYLKTHPGA) was the most immunogenic and induced the strongest CTL responses. When mice were immunized with the PAL<jats:sub>92-100<\/jats:sub>peptide plus CpG-ODN, they were protected against the lethal challenge, while control mice died within 3\u20136 days after the challenge. Consistent with lung tissue histological data, bacterial counts in the lungs of immunized mice were significantly lower than those in control mice. Also, the amino acid sequence of PAL<jats:sub>92-100<\/jats:sub>peptides is conserved among various<jats:italic>Legionella<\/jats:italic>species. To our knowledge, this study is the first to demonstrate that PAL<jats:sub>92-100<\/jats:sub>-specific CD8<jats:sup>+<\/jats:sup>T cells play a central role in the host defense response against<jats:italic>L. pneumophila<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fimmu.2020.604413","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T05:37:02Z","timestamp":1607405822000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["CD8+ T Cells Directed Against a Peptide Epitope Derived From Peptidoglycan-Associated Lipoprotein of Legionella pneumophila Confer Disease Protection"],"prefix":"10.3389","volume":"11","author":[{"given":"Sun Jin","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong-Im","family":"Sin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Ja","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(79)91219-4","article-title":"Legionnaires\u2019 disease in a prepaid medical-care group in Seattle 1963\u201375","volume":"1","author":"Foy","year":"1979","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.15.3.506-526.2002","article-title":"Legionella and Legionnaires\u2019 disease: 25 years of investigation","volume":"15","author":"Fields","year":"2002","journal-title":"Clin Microbiol Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jinf.2007.09.010","article-title":"Legionella spp. and Legionnaires\u2019 disease","volume":"56","author":"Diederen","year":"2008","journal-title":"J Infect"},{"key":"B4","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1055\/s-2000-9862","article-title":"Legionella as a cause of severe pneumonia","volume":"21","author":"Vergis","year":"2000","journal-title":"Semin Respir Crit Care Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/aem.64.9.3127-3133.1998","article-title":"Invasion of protozoa by Legionella pneumophila and its role in bacterial ecology and pathogenesis","volume":"64","author":"Abu Kwaik","year":"1998","journal-title":"Appl Environ Microbiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/0966-842x(96)10041-x","article-title":"The molecular ecology of legionellae","volume":"4","author":"Fields","year":"1996","journal-title":"Trends Microbiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/nrmicro1967","article-title":"The Legionella pneumophila replication vacuole: making a cosy niche inside host cells","volume":"7","author":"Isberg","year":"2009","journal-title":"Nat Rev Microbiol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2602","article-title":"Manipulation of host membranes by bacterial effectors","volume":"9","author":"Ham","year":"2011","journal-title":"Nat Rev Microbiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/jci110923","article-title":"Cell-mediated immunity in Legionnaires\u2019 disease","volume":"71","author":"Horwitz","year":"1983","journal-title":"J Clin Invest"},{"key":"B10","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1084\/jem.153.2.398","article-title":"Interaction of the legionnaires\u2019 disease bacterium (Legionella pneumophila) with human phagocytes. II. Antibody promotes binding of L. pneumophila to monocytes but does not inhibit intracellular multiplication","volume":"153","author":"Horwitz","year":"1981","journal-title":"J Exp Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/jci111493","article-title":"Interaction between the legionnaires\u2019 disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone","volume":"74","author":"Nash","year":"1984","journal-title":"J Clin Invest"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201948106","article-title":"Two sequential layers of antibody-mediated control of Legionella pneumophila infection","volume":"49","author":"Weber","year":"2019","journal-title":"Eur J Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/jci115065","article-title":"Vaccination with Legionella pneumophila membranes induces cell-mediated and protective immunity in a guinea pig model of Legionnaires\u2019 disease. Protective immunity independent of the major secretory protein of Legionella pneumophila","volume":"87","author":"Blander","year":"1991","journal-title":"J Clin Invest"},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.147.1.285","article-title":"Vaccination with the major secretory protein of Legionella induces humoral and cell-mediated immune responses and protective immunity across different serogroups of Legionella pneumophila and different species of Legionella","volume":"147","author":"Blander","year":"1991","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.diagmicrobio.2012.02.013","article-title":"Protective immunity against Legionnaires\u2019 disease in an A\/J mouse model using a DNA vaccine composed of an outer membrane protein (29 kDa) and the pilE fusion protein","volume":"73","author":"Xu","year":"2012","journal-title":"Diagn Microbiol Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb00824.x","article-title":"Characterization of a Legionella pneumophila gene encoding a lipoprotein antigen","volume":"5","author":"Engleberg","year":"1991","journal-title":"Mol Microbiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s100960100598","article-title":"Evaluation of the Bartels Legionella Urinary Antigen enzyme immunoassay","volume":"20","author":"Harrison","year":"2001","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.41.7.2974-2979.2003","article-title":"Characterization of a lipoprotein common to Legionella species as a urinary broad-spectrum antigen for diagnosis of Legionnaires\u2019 disease","volume":"41","author":"Kim","year":"2003","journal-title":"J Clin Microbiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2009.41.10.075","article-title":"Legionella lipoprotein activates toll-like receptor 2 and induces cytokine production and expression of costimulatory molecules in peritoneal macrophages","volume":"41","author":"Shim","year":"2009","journal-title":"Exp Mol Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1089\/104454902753604970","article-title":"Comparison of responses elicited by immunization with a Legionella species common lipoprotein delivered as naked DNA or recombinant protein","volume":"21","author":"Yoon","year":"2002","journal-title":"DNA Cell Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2018.12.014","article-title":"Induction of protective immunity by recombinant peptidoglycan associated lipoprotein (rPAL) protein of Legionella pneumophila in a BALB\/c mouse model","volume":"128","author":"Mobarez","year":"2019","journal-title":"Microb Pathog"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.7774\/cevr.2018.7.2.119","article-title":"Purification and characterization of monoclonal IgG antibodies recognizing Ebola virus glycoprotein","volume":"7","author":"Han","year":"2018","journal-title":"Clin Exp Vaccine Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-06-1838","article-title":"Therapeutic synergy of human papillomavirus E7 subunit vaccines plus cisplatin in an animal tumor model: causal involvement of increased sensitivity of cisplatin-treated tumors to CTL-mediated killing in therapeutic synergy","volume":"13","author":"Bae","year":"2007","journal-title":"Clin Cancer Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-012-1214-8","article-title":"Intratumoral electroporation of IL-12 cDNA eradicates established melanomas by Trp2 180\u2013188-specific CD8+ CTLs in a perforin\/granzyme-mediated and IFN-\u03b3-dependent manner: application of Trp2 180\u2013188 peptides","volume":"61","author":"Sin","year":"2012","journal-title":"Cancer Immunol Immunother"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/149.6.1023","article-title":"Enhanced susceptibility of cyclophosphamide-treated mice to infection with Legionella pneumophila","volume":"149","author":"Widen","year":"1984","journal-title":"J Infect Dis"},{"key":"B26","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nrc1613","article-title":"Immunotherapy and chemotherapy\u2013a practical partnership","volume":"5","author":"Lake","year":"2005","journal-title":"Nat Rev Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-011-0245-0","article-title":"Immunomodulatory effects of cyclophosphamide and implementations for vaccine design","volume":"33","author":"Sistigu","year":"2011","journal-title":"Semin Immunopathol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2011.04.011","article-title":"Immunosuppressive effect of cyclophosphamide on white blood cells and lymphocyte subpopulations from peripheral blood of Balb\/c mice","volume":"11","author":"Huyan","year":"2011","journal-title":"Int Immunopharmacol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/s0952-7915(99)80016-8","article-title":"Responses of CD8(+) T cells to intracellular bacteria","volume":"11","author":"Harty","year":"1999","journal-title":"Curr Opin Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2741\/2191","article-title":"Peptide vaccines against cancer, infectious diseases, and conception","volume":"12","author":"Naz","year":"2007","journal-title":"Front Biosci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1086\/341087","article-title":"Distribution of Legionella species and serogroups isolated by culture in patients with sporadic community-acquired legionellosis: an international collaborative survey","volume":"86","author":"Yu","year":"2002","journal-title":"J Infect Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.604413\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T19:22:46Z","timestamp":1697311366000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.604413\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,8]]},"references-count":31,"alternative-id":["10.3389\/fimmu.2020.604413"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.604413","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,8]]},"article-number":"604413"}}