{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T19:16:29Z","timestamp":1768677389511,"version":"3.49.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T00:00:00Z","timestamp":1558310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T00:00:00Z","timestamp":1558310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Malaria causes hepatic inflammation and damage, which contribute to disease severity. The pro-inflammatory cytokine interleukin (IL)-1\u03b1 is released by non-hematopoietic or hematopoietic cells during liver injury. This study established the role of IL-1\u03b1 in the liver pathology caused by blood-stage <jats:italic>P. chabaudi<\/jats:italic> malaria. During acute infection, hepatic inflammation and necrosis were accompanied by NLRP3 inflammasome-independent IL-1\u03b1 production. Systemically, IL-1\u03b1 deficiency attenuated weight loss and hypothermia but had minor effects on parasitemia control. In the liver, the absence of IL-1\u03b1 reduced the number of TUNEL<jats:sup>+<\/jats:sup> cells and necrotic lesions. This finding was associated with a lower inflammatory response, including TNF-\u03b1 production. The main source of IL-1\u03b1 in the liver of infected mice was inflammatory cells, particularly neutrophils. The implication of IL-1\u03b1 in liver inflammation and necrosis caused by <jats:italic>P. chabaudi<\/jats:italic> infection, as well as in weight loss and hypothermia, opens up new perspectives for improving malaria outcomes by inhibiting IL-1 signaling.<\/jats:p>","DOI":"10.1038\/s41598-019-44125-2","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T10:03:32Z","timestamp":1558346612000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["IL-1\u03b1 promotes liver inflammation and necrosis during blood-stage Plasmodium chabaudi malaria"],"prefix":"10.1038","volume":"9","author":[{"given":"Maria Nogueira","family":"de Menezes","sequence":"first","affiliation":[]},{"given":"\u00c9rika Machado","family":"Salles","sequence":"additional","affiliation":[]},{"given":"Fl\u00e1via","family":"Vieira","sequence":"additional","affiliation":[]},{"given":"Eduardo Pinheiro","family":"Amaral","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0023-5953","authenticated-orcid":false,"given":"Vanessa","family":"Zuzarte-Lu\u00eds","sequence":"additional","affiliation":[]},{"given":"Alexandra","family":"Cassado","sequence":"additional","affiliation":[]},{"given":"Sabrina","family":"Epiphanio","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 Maria","family":"Alvarez","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-8714","authenticated-orcid":false,"given":"Jos\u00e9 Carlos","family":"Alves-Filho","sequence":"additional","affiliation":[]},{"given":"Maria Manuel","family":"Mota","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4683-7709","authenticated-orcid":false,"given":"Maria Regina","family":"D\u2019Imp\u00e9rio-Lima","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2019,5,20]]},"reference":[{"key":"44125_CR1","unstructured":"Organization, W. H. (World Health Organization, Geneva, Switzerland, 2015)."},{"key":"44125_CR2","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/nri1311","volume":"4","author":"MM Stevenson","year":"2004","unstructured":"Stevenson, M. M. & Riley, E. M. Innate immunity to malaria. Nat Rev Immunol 4, 169\u2013180 (2004).","journal-title":"Nat Rev Immunol"},{"key":"44125_CR3","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1111\/j.1600-0676.1986.tb00304.x","volume":"6","author":"YK Joshi","year":"1986","unstructured":"Joshi, Y. K., Tandon, B. N., Acharya, S. K., Babu, S. & Tandon, M. Acute hepatic failure due to Plasmodium falciparum liver injury. Liver 6, 357\u2013360 (1986).","journal-title":"Liver"},{"key":"44125_CR4","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.jiph.2013.04.003","volume":"6","author":"A Fazil","year":"2013","unstructured":"Fazil, A. et al. Clinical profile and complication of malaria hepatopathy. Journal of infection and public health 6, 383\u2013388 (2013).","journal-title":"Journal of infection and public health"},{"key":"44125_CR5","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.jiph.2011.03.002","volume":"4","author":"H Singh","year":"2011","unstructured":"Singh, H., Parakh, A., Basu, S. & Rath, B. Plasmodium vivax malaria: is it actually benign? Journal of infection and public health 4, 91\u201395 (2011).","journal-title":"Journal of infection and public health"},{"key":"44125_CR6","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.actatropica.2016.03.031","volume":"159","author":"A Jain","year":"2016","unstructured":"Jain, A., Kaushik, R. & Kaushik, R. M. Malarial hepatopathy: Clinical profile and association with other malarial complications. Acta tropica 159, 95\u2013105 (2016).","journal-title":"Acta tropica"},{"key":"44125_CR7","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/j.mehy.2013.08.005","volume":"81","author":"YC Martins","year":"2013","unstructured":"Martins, Y. C. & Daniel-Ribeiro, C. T. A new hypothesis on the manifestation of cerebral malaria: the secret is in the liver. Medical hypotheses 81, 777\u2013783 (2013).","journal-title":"Medical hypotheses"},{"key":"44125_CR8","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1128\/IAI.01210-10","volume":"79","author":"A Haque","year":"2011","unstructured":"Haque, A. et al. High parasite burdens cause liver damage in mice following Plasmodium berghei ANKA infection independently of CD8(+) T cell-mediated immune pathology. Infect Immun 79, 1882\u20131888 (2011).","journal-title":"Infect Immun"},{"key":"44125_CR9","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/j.micinf.2013.08.001","volume":"15","author":"OC Oliveira-Lima","year":"2013","unstructured":"Oliveira-Lima, O. C., Bernardes, D., Xavier Pinto, M. C., Esteves Arantes, R. M. & Carvalho-Tavares, J. Mice lacking inducible nitric oxide synthase develop exacerbated hepatic inflammatory responses induced by Plasmodium berghei NK65 infection. Microbes Infect 15, 903\u2013910 (2013).","journal-title":"Microbes Infect"},{"key":"44125_CR10","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1645\/GE-2825.1","volume":"98","author":"Y Fu","year":"2012","unstructured":"Fu, Y., Ding, Y., Zhou, T. L., Ou, Q. Y. & Xu, W. Y. Comparative histopathology of mice infected with the 17XL and 17XNL strains of Plasmodium yoelii. J Parasitol 98, 310\u2013315 (2012).","journal-title":"J Parasitol"},{"key":"44125_CR11","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1111\/cmi.12212","volume":"16","author":"T Brugat","year":"2014","unstructured":"Brugat, T. et al. Sequestration and histopathology in Plasmodium chabaudi malaria are influenced by the immune response in an organ-specific manner. Cell Microbiol 16, 687\u2013700 (2014).","journal-title":"Cell Microbiol"},{"key":"44125_CR12","doi-asserted-by":"publisher","first-page":"26630","DOI":"10.1074\/jbc.M112.341255","volume":"287","author":"S Dey","year":"2012","unstructured":"Dey, S. et al. Impact of intravascular hemolysis in malaria on liver dysfunction: involvement of hepatic free heme overload, NF-kappaB activation, and neutrophil infiltration. J Biol Chem 287, 26630\u201326646 (2012).","journal-title":"J Biol Chem"},{"key":"44125_CR13","doi-asserted-by":"publisher","first-page":"949157","DOI":"10.1155\/2012\/949157","volume":"2012","author":"E Liaskou","year":"2012","unstructured":"Liaskou, E., Wilson, D. V. & Oo, Y. H. Innate immune cells in liver inflammation. Mediators Inflamm 2012, 949157 (2012).","journal-title":"Mediators Inflamm"},{"key":"44125_CR14","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1002\/eji.201141550","volume":"41","author":"CA Dinarello","year":"2011","unstructured":"Dinarello, C. A. A clinical perspective of IL-1\u03b2 as the gatekeeper of inflammation. Eur J Immunol 41, 1203\u20131217 (2011).","journal-title":"Eur J Immunol"},{"key":"44125_CR15","doi-asserted-by":"publisher","first-page":"4835","DOI":"10.4049\/jimmunol.1102048","volume":"187","author":"P Rider","year":"2011","unstructured":"Rider, P. et al. IL-1\u03b1 and IL-1\u03b2 recruit different myeloid cells and promote different stages of sterile inflammation. J Immunol 187, 4835\u20134843 (2011).","journal-title":"J Immunol"},{"key":"44125_CR16","doi-asserted-by":"publisher","first-page":"4624","DOI":"10.1073\/pnas.74.10.4624","volume":"74","author":"CA Dinarello","year":"1977","unstructured":"Dinarello, C. A., Renfer, L. & Wolff, S. M. Human leukocytic pyrogen: purification and development of a radioimmunoassay. Proc Natl Acad Sci USA 74, 4624\u20134627 (1977).","journal-title":"Proc Natl Acad Sci USA"},{"key":"44125_CR17","doi-asserted-by":"publisher","first-page":"2574","DOI":"10.1073\/pnas.0915018107","volume":"107","author":"I Cohen","year":"2010","unstructured":"Cohen, I. et al. Differential release of chromatin-bound IL-1alpha discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc Natl Acad Sci USA 107, 2574\u20132579 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"44125_CR18","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.ccr.2008.06.016","volume":"14","author":"T Sakurai","year":"2008","unstructured":"Sakurai, T. et al. Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis. Cancer Cell 14, 156\u2013165 (2008).","journal-title":"Cancer Cell"},{"key":"44125_CR19","doi-asserted-by":"crossref","unstructured":"Zhang, C. et al. Macrophage-derived IL-1alpha promotes sterile inflammation in a mouse model of acetaminophen hepatotoxicity. Cell Mol Immunol (2018).","DOI":"10.1038\/cmi.2017.22"},{"key":"44125_CR20","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1038\/nm1603","volume":"13","author":"CJ Chen","year":"2007","unstructured":"Chen, C. J. et al. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med 13, 851\u2013856 (2007).","journal-title":"Nat Med"},{"key":"44125_CR21","doi-asserted-by":"crossref","unstructured":"Gehrke, N. et al. Hepatocyte-specific deletion of IL1-RI attenuates liver injury by blocking IL-1 driven autoinflammation. J Hepatol (2018).","DOI":"10.1016\/j.jhep.2018.01.008"},{"key":"44125_CR22","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.dld.2014.01.156","volume":"46","author":"S Olteanu","year":"2014","unstructured":"Olteanu, S. et al. Lack of interleukin-1alpha in Kupffer cells attenuates liver inflammation and expression of inflammatory cytokines in hypercholesterolaemic mice. Dig Liver Dis 46, 433\u2013439 (2014).","journal-title":"Dig Liver Dis"},{"key":"44125_CR23","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.immuni.2012.01.018","volume":"36","author":"O Gross","year":"2012","unstructured":"Gross, O. et al. Inflammasome activators induce interleukin-1alpha secretion via distinct pathways with differential requirement for the protease function of caspase-1. Immunity 36, 388\u2013400 (2012).","journal-title":"Immunity"},{"key":"44125_CR24","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/gene.2012.25","volume":"13","author":"SJ Dunstan","year":"2012","unstructured":"Dunstan, S. J. et al. Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese. Genes Immun 13, 503\u2013508 (2012).","journal-title":"Genes Immun"},{"key":"44125_CR25","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/0140-6736(90)92827-5","volume":"336","author":"D Kwiatkowski","year":"1990","unstructured":"Kwiatkowski, D. et al. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 336, 1201\u20131204 (1990).","journal-title":"Lancet"},{"key":"44125_CR26","doi-asserted-by":"publisher","first-page":"735","DOI":"10.4269\/ajtmh.1994.50.735","volume":"50","author":"KA Rockett","year":"1994","unstructured":"Rockett, K. A., Awburn, M. M., Rockett, E. J. & Clark, I. A. Tumor necrosis factor and interleukin-1 synergy in the context of malaria pathology. Am J Trop Med Hyg 50, 735\u2013742 (1994).","journal-title":"Am J Trop Med Hyg"},{"key":"44125_CR27","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1046\/j.1365-2613.1999.00101.x","volume":"80","author":"R Sinniah","year":"1999","unstructured":"Sinniah, R., Rui-Mei, L. & Kara, A. Up-regulation of cytokines in glomerulonephritis associated with murine malaria infection. Int J Exp Pathol 80, 87\u201395 (1999).","journal-title":"Int J Exp Pathol"},{"key":"44125_CR28","doi-asserted-by":"publisher","first-page":"e1003885","DOI":"10.1371\/journal.ppat.1003885","volume":"10","author":"MA Ataide","year":"2014","unstructured":"Ataide, M. A. et al. Malaria-induced NLRP12\/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection. PLoS Pathog 10, e1003885 (2014).","journal-title":"PLoS Pathog"},{"key":"44125_CR29","doi-asserted-by":"publisher","first-page":"e0184084","DOI":"10.1371\/journal.pone.0184084","volume":"12","author":"M Sultan","year":"2017","unstructured":"Sultan, M. et al. Interleukin-1alpha and Interleukin-1beta play a central role in the pathogenesis of fulminant hepatic failure in mice. PLoS One 12, e0184084 (2017).","journal-title":"PLoS One"},{"key":"44125_CR30","doi-asserted-by":"publisher","first-page":"e1004598","DOI":"10.1371\/journal.ppat.1004598","volume":"11","author":"H Borges da Silva","year":"2015","unstructured":"Borges da Silva, H. et al. In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria. PLoS Pathog 11, e1004598 (2015).","journal-title":"PLoS Pathog"},{"key":"44125_CR31","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1111\/j.1462-5822.2011.01741.x","volume":"14","author":"HA Del Portillo","year":"2012","unstructured":"Del Portillo, H. A. et al. The role of the spleen in malaria. Cell Microbiol 14, 343\u2013355 (2012).","journal-title":"Cell Microbiol"},{"key":"44125_CR32","doi-asserted-by":"publisher","first-page":"4399","DOI":"10.1128\/IAI.68.8.4399-4406.2000","volume":"68","author":"Z Su","year":"2000","unstructured":"Su, Z. & Stevenson, M. M. Central role of endogenous gamma interferon in protective immunity against blood-stage Plasmodium chabaudi AS infection. Infect Immun 68, 4399\u20134406 (2000).","journal-title":"Infect Immun"},{"key":"44125_CR33","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1002\/hep.24802","volume":"55","author":"A Ambade","year":"2012","unstructured":"Ambade, A., Catalano, D., Lim, A. & Mandrekar, P. Inhibition of heat shock protein (molecular weight 90 kDa) attenuates proinflammatory cytokines and prevents lipopolysaccharide-induced liver injury in mice. Hepatology 55, 1585\u20131595 (2012).","journal-title":"Hepatology"},{"key":"44125_CR34","doi-asserted-by":"publisher","first-page":"e22434","DOI":"10.1371\/journal.pone.0022434","volume":"6","author":"SM Muxel","year":"2011","unstructured":"Muxel, S. M. et al. The spleen CD4+ T cell response to blood-stage Plasmodium chabaudi malaria develops in two phases characterized by different properties. PLoS One 6, e22434 (2011).","journal-title":"PLoS One"},{"key":"44125_CR35","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-13-106","volume":"13","author":"P Viriyavejakul","year":"2014","unstructured":"Viriyavejakul, P., Khachonsaksumet, V. & Punsawad, C. Liver changes in severe Plasmodium falciparum malaria: histopathology, apoptosis and nuclear factor kappa B expression. Malar J 13, 106 (2014).","journal-title":"Malar J"},{"key":"44125_CR36","doi-asserted-by":"publisher","first-page":"15837","DOI":"10.1073\/pnas.0903419106","volume":"106","author":"E Seixas","year":"2009","unstructured":"Seixas, E. et al. Heme oxygenase-1 affords protection against noncerebral forms of severe malaria. Proc Natl Acad Sci USA 106, 15837\u201315842 (2009).","journal-title":"Proc Natl Acad Sci USA"},{"key":"44125_CR37","doi-asserted-by":"publisher","first-page":"e01300","DOI":"10.1128\/mBio.01300-15","volume":"7","author":"CM Feintuch","year":"2016","unstructured":"Feintuch, C. M. et al. Activated Neutrophils Are Associated with Pediatric Cerebral Malaria Vasculopathy in Malawian Children. MBio 7, e01300\u201301315 (2016).","journal-title":"MBio"},{"key":"44125_CR38","doi-asserted-by":"publisher","first-page":"e1006054","DOI":"10.1371\/journal.ppat.1006054","volume":"12","author":"MK Sercundes","year":"2016","unstructured":"Sercundes, M. K. et al. Targeting Neutrophils to Prevent Malaria-Associated Acute Lung Injury\/Acute Respiratory Distress Syndrome in Mice. PLoS Pathog 12, e1006054 (2016).","journal-title":"PLoS Pathog"},{"key":"44125_CR39","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.1016\/j.celrep.2015.11.055","volume":"13","author":"BC Rocha","year":"2015","unstructured":"Rocha, B. C. et al. Type I Interferon Transcriptional Signature in Neutrophils and Low-Density Granulocytes Are Associated with Tissue Damage in Malaria. Cell Rep 13, 2829\u20132841 (2015).","journal-title":"Cell Rep"},{"key":"44125_CR40","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1002\/eji.1830230824","volume":"23","author":"HS Oldenburg","year":"1993","unstructured":"Oldenburg, H. S. et al. Cachexia and the acute-phase protein response in inflammation are regulated by interleukin-6. Eur J Immunol 23, 1889\u20131894 (1993).","journal-title":"Eur J Immunol"},{"key":"44125_CR41","doi-asserted-by":"publisher","first-page":"4850","DOI":"10.1128\/IAI.71.9.4850-4856.2003","volume":"71","author":"C Li","year":"2003","unstructured":"Li, C., Sanni, L. A., Omer, F., Riley, E. & Langhorne, J. Pathology of Plasmodium chabaudi chabaudi infection and mortality in interleukin-10-deficient mice are ameliorated by anti-tumor necrosis factor alpha and exacerbated by anti-transforming growth factor beta antibodies. Infect Immun 71, 4850\u20134856 (2003).","journal-title":"Infect Immun"},{"key":"44125_CR42","doi-asserted-by":"publisher","first-page":"15342","DOI":"10.1074\/jbc.M112.439547","volume":"288","author":"C Sanz-Garcia","year":"2013","unstructured":"Sanz-Garcia, C. et al. Sterile inflammation in acetaminophen-induced liver injury is mediated by Cot\/tpl2. J Biol Chem 288, 15342\u201315351 (2013).","journal-title":"J Biol Chem"},{"issue":"Suppl 2","key":"44125_CR43","doi-asserted-by":"publisher","first-page":"ii96","DOI":"10.1136\/annrheumdis-2012-202252","volume":"72","author":"AS Yazdi","year":"2013","unstructured":"Yazdi, A. S. & Drexler, S. K. Regulation of interleukin 1alpha secretion by inflammasomes. Ann Rheum Dis 72(Suppl 2), ii96\u201399 (2013).","journal-title":"Ann Rheum Dis"},{"key":"44125_CR44","doi-asserted-by":"publisher","first-page":"4135","DOI":"10.1128\/IAI.68.7.4135-4144.2000","volume":"68","author":"MM Mota","year":"2000","unstructured":"Mota, M. M., Jarra, W., Hirst, E., Patnaik, P. K. & Holder, A. A. Plasmodium chabaudi-infected erythrocytes adhere to CD36 and bind to microvascular endothelial cells in an organ-specific way. Infect Immun 68, 4135\u20134144 (2000).","journal-title":"Infect Immun"},{"key":"44125_CR45","doi-asserted-by":"publisher","first-page":"e1004625","DOI":"10.1371\/journal.ppat.1004625","volume":"11","author":"AK Caffrey","year":"2015","unstructured":"Caffrey, A. K. et al. IL-1alpha signaling is critical for leukocyte recruitment after pulmonary Aspergillus fumigatus challenge. PLoS Pathog 11, e1004625 (2015).","journal-title":"PLoS Pathog"},{"key":"44125_CR46","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1002\/eji.201445195","volume":"45","author":"D Lin","year":"2015","unstructured":"Lin, D. et al. Secreted IL-1alpha promotes T-cell activation and expansion of CD11b(+) Gr1(+) cells in carbon tetrachloride-induced liver injury in mice. Eur J Immunol 45, 2084\u20132098 (2015).","journal-title":"Eur J Immunol"},{"key":"44125_CR47","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1016\/j.jhep.2015.05.012","volume":"63","author":"M Kandel-Kfir","year":"2015","unstructured":"Kandel-Kfir, M. et al. Interleukin-1alpha deficiency attenuates endoplasmic reticulum stress-induced liver damage and CHOP expression in mice. J Hepatol 63, 926\u2013933 (2015).","journal-title":"J Hepatol"},{"key":"44125_CR48","doi-asserted-by":"crossref","first-page":"15836","DOI":"10.1016\/S0021-9258(19)49611-7","volume":"267","author":"E Stylianou","year":"1992","unstructured":"Stylianou, E. et al. Interleukin 1 induces NF-kappa B through its type I but not its type II receptor in lymphocytes. J Biol Chem 267, 15836\u201315841 (1992).","journal-title":"J Biol Chem"},{"key":"44125_CR49","doi-asserted-by":"publisher","first-page":"5928","DOI":"10.4049\/jimmunol.167.10.5928","volume":"167","author":"K Adachi","year":"2001","unstructured":"Adachi, K. et al. Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor\/myeloid differentiation factor 88-dependent mechanism. J Immunol 167, 5928\u20135934 (2001).","journal-title":"J Immunol"},{"key":"44125_CR50","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1128\/iai.59.1.51-58.1991","volume":"59","author":"JE Podoba","year":"1991","unstructured":"Podoba, J. E. & Stevenson, M. M. CD4+ and CD8+ T lymphocytes both contribute to acquired immunity to blood-stage Plasmodium chabaudi AS. Infect Immun 59, 51\u201358 (1991).","journal-title":"Infect Immun"},{"key":"44125_CR51","doi-asserted-by":"publisher","first-page":"5S","DOI":"10.1177\/0192623310386499","volume":"38","author":"B Thoolen","year":"2010","unstructured":"Thoolen, B. et al. Proliferative and nonproliferative lesions of the rat and mouse hepatobiliary system. Toxicol Pathol 38, 5S\u201381S (2010).","journal-title":"Toxicol Pathol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-44125-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-44125-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-44125-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T09:38:58Z","timestamp":1671269938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-44125-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,20]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["44125"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-44125-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,20]]},"assertion":[{"value":"8 February 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7575"}}