{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:20:35Z","timestamp":1792138835442,"version":"4.4.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"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":[[2015,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Melioidosis, a severe human disease caused by the bacterium Burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicemia to chronic localized illness or latent infection. Murine models have been widely used to study the pathogenesis of infection and to evaluate novel therapies or vaccines, but how faithfully they recapitulate the biology of human melioidosis at a molecular level is not known. In this study, mice were intranasally infected with either high or low doses of B. pseudomallei to generate either acute, chronic, or latent infection and host blood and tissue transcriptional profiles were generated. Acute infection was accompanied by a homogeneous signature associated with induction of multiple innate immune response pathways, such as IL-10, TREM1, and IFN signaling, largely found in both blood and tissue. The transcriptional profile in blood reflected the heterogeneity of chronic infection and quantitatively reflected the severity of disease. Genes associated with fibrosis and tissue remodeling, including matrix metalloproteases and collagen, were upregulated in chronically infected mice with severe disease. Transcriptional signatures of both acute and chronic melioidosis revealed upregulation of iNOS in tissue, consistent with the expression of IFN-\u03b3, but also Arginase-1, a functional antagonist of the iNOS pathway, and was confirmed by immunohistochemistry. Comparison of these mouse blood datasets by pathway and modular analysis with the blood transcriptional signature of patients with melioidosis showed that many genes were similarly perturbed, including Arginase-1, IL-10, TREM1, and IFN signaling, revealing the common immune response occurring in both mice and humans.<\/jats:p>","DOI":"10.4049\/jimmunol.1500641","type":"journal-article","created":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T01:59:27Z","timestamp":1440640767000},"page":"3248-3261","source":"Crossref","is-referenced-by-count":20,"title":["The Blood Transcriptome of Experimental Melioidosis Reflects Disease Severity and Shows Considerable Similarity with the Human Disease"],"prefix":"10.1093","volume":"195","author":[{"given":"Laura","family":"Conejero","sequence":"first","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Potempa","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, Mill Hill Laboratory , London NW7 1AA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M","family":"Graham","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, Mill Hill Laboratory , London NW7 1AA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Spink","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Blankley","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, Mill Hill Laboratory , London NW7 1AA ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J","family":"Salguero","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, University of Surrey , Guildford GU2 7XH ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rungnapa","family":"Pankla-Sranujit","sequence":"additional","affiliation":[{"name":"Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University , Khon Kaen 40002 ,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasong","family":"Khaenam","sequence":"additional","affiliation":[{"name":"Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University , Khon Kaen 40002 ,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques F","family":"Banchereau","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory , Farmington, CT 06030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Pascual","sequence":"additional","affiliation":[{"name":"Baylor Institute for Immunology Research , Dallas, TX 75204"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Chaussabel","sequence":"additional","affiliation":[{"name":"Systems Biology Department, Sidra Medical and Research Center , Doha ,","place":["Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganjana","family":"Lertmemongkolchai","sequence":"additional","affiliation":[{"name":"Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University , Khon Kaen 40002 ,","place":["Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"O\u2019Garra","sequence":"additional","affiliation":[{"name":"The Francis Crick Institute, Mill Hill Laboratory , London NW7 1AA ,","place":["United Kingdom"]},{"name":"National Heart and Lung Institute, St. Mary\u2019s Hospital, Imperial College London , London SW7 2AZ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J","family":"Bancroft","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London WC1E 7HT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,10,1]]},"reference":[{"key":"2025030704154568300_r1","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nrmicro1385","article-title":"Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei","volume":"4","author":"Wiersinga","year":"2006","journal-title":"Nat. Rev. Microbiol."},{"key":"2025030704154568300_r2","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1056\/NEJMra1204699","article-title":"Melioidosis","volume":"367","author":"Wiersinga","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"2025030704154568300_r3","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1128\/iai.60.6.2402-2408.1992","article-title":"Prolonged elevation of interleukin-8 and interleukin-6 concentrations in plasma and of leukocyte interleukin-8 mRNA levels during septicemic and localized Pseudomonas pseudomallei infection","volume":"60","author":"Friedland","year":"1992","journal-title":"Infect. Immun."},{"key":"2025030704154568300_r4","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1086\/315155","article-title":"Elevated plasma concentrations of interferon (IFN)- \u03b3 and the IFN-\u03b3\u2011inducing cytokines interleukin (IL)-18, IL-12, and IL-15 in severe melioidosis","volume":"180","author":"Lauw","year":"1999","journal-title":"J. Infect. Dis."},{"key":"2025030704154568300_r5","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1016\/S0140-6736(03)13374-0","article-title":"Melioidosis","volume":"361","author":"White","year":"2003","journal-title":"Lancet"},{"key":"2025030704154568300_r6","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1086\/507632","article-title":"Risk factors for recurrent melioidosis in northeast Thailand","volume":"43","author":"Limmathurotsakul","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"2025030704154568300_r7","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1378\/chest.68.2.261","article-title":"Melioidosis: recrudescence associated with bronchogenic carcinoma twenty-six years following initial geographic exposure","volume":"68","author":"Mays","year":"1975","journal-title":"Chest"},{"key":"2025030704154568300_r8","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1086\/498983","article-title":"Role of T cells in innate and adaptive immunity against murine Burkholderia pseudomallei infection","volume":"193","author":"Haque","year":"2006","journal-title":"J. Infect. Dis."},{"key":"2025030704154568300_r9","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1099\/jmm.0.47596-0","article-title":"Burkholderia pseudomallei aerosol infection results in differential inflammatory responses in BALB\/c and C57Bl\/6 mice","volume":"57","author":"Tan","year":"2008","journal-title":"J. Med. Microbiol."},{"key":"2025030704154568300_r10","doi-asserted-by":"crossref","first-page":"S111","DOI":"10.1016\/S0035-9203(08)70026-9","article-title":"Burkholderia pseudomallei: animal models of infection","volume":"102","author":"Titball","year":"2008","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"2025030704154568300_r11","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ajpath.2011.03.031","article-title":"Low-dose exposure of C57BL\/6 mice to burkholderia pseudomallei mimics chronic human melioidosis","volume":"179","author":"Conejero","year":"2011","journal-title":"Am. J. Pathol."},{"key":"2025030704154568300_r12","doi-asserted-by":"crossref","first-page":"6300","DOI":"10.1128\/IAI.00966-06","article-title":"Role of inducible nitric oxide synthase and NADPH oxidase in early control of Burkholderia pseudomallei infection in mice","volume":"74","author":"Breitbach","year":"2006","journal-title":"Infect. Immun."},{"key":"2025030704154568300_r13","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/cid\/ciq192","article-title":"Glyburide is anti-inflammatory and associated with reduced mortality in melioidosis","volume":"52","author":"Koh","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"2025030704154568300_r14","doi-asserted-by":"crossref","first-page":"e54961","DOI":"10.1371\/journal.pone.0054961","article-title":"Host responses to melioidosis and tuberculosis are both dominated by interferon-mediated signaling","volume":"8","author":"Koh","year":"2013","journal-title":"PLoS One"},{"key":"2025030704154568300_r15","doi-asserted-by":"crossref","first-page":"R127","DOI":"10.1186\/gb-2009-10-11-r127","article-title":"Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis","volume":"10","author":"Pankla","year":"2009","journal-title":"Genome Biol."},{"key":"2025030704154568300_r16","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1186\/1471-2164-11-672","article-title":"Genome wide transcriptome profiling of a murine acute melioidosis model reveals new insights into how Burkholderia pseudomallei overcomes host innate immunity","volume":"11","author":"Chin","year":"2010","journal-title":"BMC Genomics"},{"key":"2025030704154568300_r17","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.immuni.2008.05.012","article-title":"A modular analysis framework for blood genomics studies: application to systemic lupus erythematosus","volume":"29","author":"Chaussabel","year":"2008","journal-title":"Immunity"},{"key":"2025030704154568300_r18","doi-asserted-by":"crossref","DOI":"10.1165\/rcmb.2014-0366OC","article-title":"Role of Chitinase 3-like-1 in IL-18\u2011induced pulmonary type-1, -2 and -17 inflammation, alveolar destruction and airway fibrosis in the murine lung","author":"Kang","year":"2015","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2025030704154568300_r19","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1146\/annurev-pathol-020712-163930","article-title":"Host responses in tissue repair and fibrosis","volume":"8","author":"Duffield","year":"2013","journal-title":"Annu. Rev. Pathol."},{"key":"2025030704154568300_r20","doi-asserted-by":"crossref","first-page":"3593","DOI":"10.1128\/IAI.67.7.3593-3600.1999","article-title":"Obligatory role of \u03b3 interferon for host survival in a murine model of infection with Burkholderia pseudomallei","volume":"67","author":"Santanirand","year":"1999","journal-title":"Infect. Immun."},{"key":"2025030704154568300_r21","doi-asserted-by":"crossref","first-page":"e407","DOI":"10.1371\/journal.pntd.0000407","article-title":"Phenotypic and functional characterization of human memory T cell responses to Burkholderia pseudomallei","volume":"3","author":"Tippayawat","year":"2009","journal-title":"PLoS Negl. Trop. Dis."},{"key":"2025030704154568300_r22","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/nature09247","article-title":"An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis","volume":"466","author":"Berry","year":"2010","journal-title":"Nature"},{"key":"2025030704154568300_r23","doi-asserted-by":"crossref","first-page":"e70630","DOI":"10.1371\/journal.pone.0070630","article-title":"Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers","volume":"8","author":"Bloom","year":"2013","journal-title":"PLoS One"},{"key":"2025030704154568300_r24","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.micinf.2008.04.019","article-title":"Gene-expression profiles in murine melioidosis","volume":"10","author":"Wiersinga","year":"2008","journal-title":"Microbes Infect."},{"key":"2025030704154568300_r25","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1086\/509810","article-title":"A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei","volume":"195","author":"Easton","year":"2007","journal-title":"J. Infect. Dis."},{"key":"2025030704154568300_r26","doi-asserted-by":"crossref","first-page":"e248","DOI":"10.1371\/journal.pmed.0040248","article-title":"Toll-like receptor 2 impairs host defense in gram-negative sepsis caused by Burkholderia pseudomallei (Melioidosis)","volume":"4","author":"Wiersinga","year":"2007","journal-title":"PLoS Med."},{"key":"2025030704154568300_r27","doi-asserted-by":"crossref","first-page":"5520","DOI":"10.4049\/jimmunol.1500312","article-title":"Mature cystic fibrosis airway neutrophils suppress T cell function: evidence for a role of arginase 1 but not programmed death-ligand 1","volume":"194","author":"Ingersoll","year":"2015","journal-title":"J. Immunol."},{"key":"2025030704154568300_r28","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1111\/j.1476-5381.2009.00291.x","article-title":"Arginase: an emerging key player in the mammalian immune system","volume":"158","author":"Munder","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"2025030704154568300_r29","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1002\/eji.200839041","article-title":"l-Arginine deprivation impairs Leishmania major\u2011specific T-cell responses","volume":"39","author":"Munder","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"2025030704154568300_r30","doi-asserted-by":"crossref","first-page":"e480","DOI":"10.1371\/journal.pntd.0000480","article-title":"Local suppression of T cell responses by arginase-induced l-arginine depletion in nonhealing leishmaniasis","volume":"3","author":"Modolell","year":"2009","journal-title":"PLoS Negl. Trop. Dis."},{"key":"2025030704154568300_r31","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1073\/pnas.1222878110","article-title":"Genomic responses in mouse models poorly mimic human inflammatory diseases","volume":"110","author":"Seok","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/195\/7\/3248\/62249006\/1500641.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/195\/7\/3248\/62249006\/1500641.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T04:33:02Z","timestamp":1741321982000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/195\/7\/3248\/7973359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,1]]},"references-count":31,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2015,10,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1500641","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,10]]},"published":{"date-parts":[[2015,10,1]]}}}