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Although the roles of cytokines such as TNF-\u03b1, IL-12, IFN-\u03b3, and IL-10 in immunity and pathogenesis to the blood stage malaria are largely known, the role of IL-4 remains less understood. IL-4 targets many cell types and induces multiple effects, including cell proliferation, gene expression, protection from apoptosis, and immune regulation. Accordingly, IL-4 has been exploited as a therapeutic for several inflammatory diseases. Malaria caused by Plasmodium falciparum manifests in many organ-specific fatal pathologies, including cerebral malaria (CM), driven by a high parasite load, leading to parasite sequestration in organs and consequent excessive inflammatory responses and endothelial damage. We investigated the therapeutic potential of IL-4 against fatal malaria in Plasmodium berghei ANKA\u2013infected C57BL\/6J mice, an experimental CM model. IL-4 treatment significantly reduced parasitemia, CM pathology, and mortality. The therapeutic effect of IL-4 is mediated through multiple mechanisms, including enhanced parasite clearance mediated by upregulation of phagocytic receptors and increased IgM production, and decreased brain inflammatory responses, including reduced chemokine (CXCL10) production, reduced chemokine receptor (CXCR3) and adhesion molecule (LFA-1) expression by T cells, and downregulation of cytotoxic T cell lytic potential. IL-4 treatment markedly reduced the infiltration of CD8+ T cells and brain pathology. STAT6, PI3K\u2013Akt\u2013NF-\u03baB, and Src signaling mediated the cellular and molecular events that contributed to the IL-4\u2013dependent decrease in parasitemia. Overall, our results provide mechanistic insights into how IL-4 treatment mitigates experimental CM and have implications in developing treatment strategies for organ-specific fatal malaria.<\/jats:p>","DOI":"10.4049\/jimmunol.2000779","type":"journal-article","created":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T23:55:14Z","timestamp":1606348514000},"page":"118-131","source":"Crossref","is-referenced-by-count":20,"title":["IL-4 Treatment Mitigates Experimental Cerebral Malaria by Reducing Parasitemia, Dampening Inflammation, and Lessening the Cytotoxicity of T Cells"],"prefix":"10.1093","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6892-378X","authenticated-orcid":false,"given":"Xianzhu","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine , Hershey, PA 17033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8935-6780","authenticated-orcid":false,"given":"Ramesh P","family":"Thylur","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine , Hershey, PA 17033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4665-6243","authenticated-orcid":false,"given":"Kiran K","family":"Dayanand","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine , Hershey, PA 17033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishore","family":"Punnath","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine , Hershey, PA 17033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C","family":"Norbury","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine , Hershey, PA 17033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6860-5108","authenticated-orcid":false,"given":"D Channe","family":"Gowda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine , Hershey, PA 17033"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,1]]},"reference":[{"key":"2025022610324982400_r1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0140-6736(12)60034-8","article-title":"Global malaria mortality between 1980 and 2010: a systematic analysis","volume":"379","author":"Murray","year":"2012","journal-title":"Lancet"},{"key":"2025022610324982400_r2","doi-asserted-by":"crossref","DOI":"10.30875\/7e6f8c91-en","volume-title":"World Malaria Report 2019.","author":"World Health Organization","year":"2019"},{"key":"2025022610324982400_r3","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1128\/CMR.00074-12","article-title":"Evidence and implications of mortality associated with acute Plasmodium vivax malaria","volume":"26","author":"Baird","year":"2013","journal-title":"Clin. Microbiol. Rev."},{"key":"2025022610324982400_r4","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a025619","article-title":"Antimalarial drug resistance: a threat to malaria elimination","volume":"7","author":"Menard","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"2025022610324982400_r5","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1056\/NEJMoa1515257","article-title":"Seven-year efficacy of RTS,S\/AS01 malaria vaccine among young African children","volume":"374","author":"Olotu","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"2025022610324982400_r6","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1056\/NEJMoa1505819","article-title":"Genetic diversity and protective efficacy of the RTS,S\/AS01 malaria vaccine","volume":"373","author":"Neafsey","year":"2015","journal-title":"N. Engl. J. 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Microbiol."},{"key":"2025022610324982400_r10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1365-3024.2006.00775.x","article-title":"Regulating immunity to malaria","volume":"28","author":"Riley","year":"2006","journal-title":"Parasite Immunol."},{"key":"2025022610324982400_r11","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1146\/annurev.immunol.17.1.701","article-title":"The IL-4 receptor: signaling mechanisms and biologic functions","volume":"17","author":"Nelms","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"2025022610324982400_r12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1615\/CritRevImmunol.v17.i1.10","article-title":"Functions of IL-4 and control of its expression","volume":"17","author":"Brown","year":"1997","journal-title":"Crit. Rev. 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Immunol."},{"key":"2025022610324982400_r32","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.actatropica.2003.11.014","article-title":"IL4-589C\/T polymorphism and IgE levels in severe malaria","volume":"90","author":"Verra","year":"2004","journal-title":"Acta Trop."},{"key":"2025022610324982400_r33","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1128\/IAI.72.1.322-331.2004","article-title":"Mice deficient in interleukin-4 (IL-4) or IL-4 receptor \u03b1 have higher resistance to sporozoite infection with Plasmodium berghei (ANKA) than do naive wild-type mice","volume":"72","author":"Saeftel","year":"2004","journal-title":"Infect. 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Immunol."},{"key":"2025022610324982400_r35","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.actatropica.2007.02.008","article-title":"Relative levels of IL4 and IFN-\u03b3 in complicated malaria: association with IL4 polymorphism and peripheral parasitemia","volume":"101","author":"Tangteerawatana","year":"2007","journal-title":"Acta Trop."},{"key":"2025022610324982400_r36","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1179\/2295333715Y.0000000042","article-title":"Correlation of interleukin-4 levels with Plasmodium falciparum malaria parasitaemia in Sudanese children","volume":"70","author":"Elhussein","year":"2015","journal-title":"Acta Clin. Belg."},{"key":"2025022610324982400_r37","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00281-015-0476-6","article-title":"Pathogenic CD8+ T cells in experimental cerebral malaria","volume":"37","author":"Howland","year":"2015","journal-title":"Semin. Immunopathol."},{"key":"2025022610324982400_r38","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s11011-015-9787-5","article-title":"Cerebral malaria--clinical manifestations and pathogenesis","volume":"31","author":"Hora","year":"2016","journal-title":"Metab. Brain Dis."},{"key":"2025022610324982400_r39","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1172\/JCI133474","article-title":"CD8+ T cells target cerebrovasculature in children with cerebral malaria","volume":"130","author":"Riggle","year":"2020","journal-title":"J. Clin. Invest."},{"key":"2025022610324982400_r40","doi-asserted-by":"crossref","first-page":"327","DOI":"10.4049\/jimmunol.1900829","article-title":"Desperately seeking therapies for cerebral malaria","volume":"204","author":"Riggle","year":"2020","journal-title":"J. Immunol."},{"key":"2025022610324982400_r41","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0166-6851(96)02584-4","article-title":"A method for the quantitative assessment of malaria parasite development in organs of the mammalian host","volume":"77","author":"Hulier","year":"1996","journal-title":"Mol. Biochem. Parasitol."},{"key":"2025022610324982400_r42","doi-asserted-by":"crossref","first-page":"4338","DOI":"10.4049\/jimmunol.0903824","article-title":"Protein-DNA complex is the exclusive malaria parasite component that activates dendritic cells and triggers innate immune responses","volume":"184","author":"Wu","year":"2010","journal-title":"J. Immunol."},{"key":"2025022610324982400_r43","doi-asserted-by":"crossref","first-page":"5073","DOI":"10.4049\/jimmunol.1102143","article-title":"TLR9 and MyD88 are crucial for the development of protective immunity to malaria","volume":"188","author":"Gowda","year":"2012","journal-title":"J. Immunol."},{"key":"2025022610324982400_r44","doi-asserted-by":"crossref","first-page":"13615","DOI":"10.1074\/jbc.M116.770313","article-title":"Small molecule-based inhibition of MEK1\/2 proteins dampens inflammatory responses to malaria, reduces parasite load, and mitigates pathogenic outcomes","volume":"292","author":"Wu","year":"2017","journal-title":"J. Biol. Chem."},{"key":"2025022610324982400_r45","article-title":"Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. [Published erratum appears in 2005 PLoS Med. 2: 390.]","volume":"2","author":"Dondorp","year":"2005","journal-title":"PLoS Med."},{"key":"2025022610324982400_r46","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0175328","article-title":"Influence of host factors and parasite biomass on the severity of imported Plasmodium falciparum malaria","volume":"12","author":"Argy","year":"2017","journal-title":"PLoS One"},{"key":"2025022610324982400_r47","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jinf.2013.04.013","article-title":"Comparison of parasite sequestration in uncomplicated and severe childhood Plasmodium falciparum malaria","volume":"67","author":"Cunnington","year":"2013","journal-title":"J. Infect."},{"key":"2025022610324982400_r48","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.pt.2004.11.008","article-title":"The importance of the spleen in malaria","volume":"21","author":"Engwerda","year":"2005","journal-title":"Trends Parasitol."},{"key":"2025022610324982400_r49","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1128\/IAI.02398-14","article-title":"Acquisition of antibodies against Plasmodium falciparum merozoites and malaria immunity in young children and the influence of age, force of infection, and magnitude of response","volume":"83","author":"Stanisic","year":"2015","journal-title":"Infect. Immun."},{"key":"2025022610324982400_r50","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4049\/jimmunol.1400844","article-title":"Natural antibodies bridge innate and adaptive immunity","volume":"194","author":"Panda","year":"2015","journal-title":"J. Immunol."},{"key":"2025022610324982400_r51","doi-asserted-by":"crossref","first-page":"466","DOI":"10.5114\/ceji.2018.81354","article-title":"Natural antibodies - facts known and unknown","volume":"43","author":"Palma","year":"2018","journal-title":"Cent. Eur. J. Immunol."},{"key":"2025022610324982400_r52","first-page":"403","article-title":"Immunopathological aspects of Plasmodium berghei infection in five strains of mice. I. Immune complexes and other serological features during the infection","volume":"42","author":"Contreras","year":"1980","journal-title":"Clin. Exp. Immunol."},{"key":"2025022610324982400_r53","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/cmi.12403","article-title":"Investigating the function of Fc-specific binding of IgM to Plasmodium falciparum erythrocyte membrane protein 1 mediating erythrocyte rosetting","volume":"17","author":"Stevenson","year":"2015","journal-title":"Cell. Microbiol."},{"key":"2025022610324982400_r54","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.pt.2015.09.007","article-title":"Immunoglobulin M: restrainer of inflammation and mediator of immune evasion by Plasmodium falciparum malaria","volume":"32","author":"Pleass","year":"2016","journal-title":"Trends Parasitol."},{"key":"2025022610324982400_r55","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1365-3024.2005.00760.x","article-title":"Parasite-specific IgM plays a significant role in the protective immune response to asexual erythrocytic stage Plasmodium chabaudi AS infection","volume":"27","author":"Couper","year":"2005","journal-title":"Parasite Immunol."},{"key":"2025022610324982400_r56","doi-asserted-by":"crossref","first-page":"4967","DOI":"10.4049\/jimmunol.1003021","article-title":"Natural IgM is required for suppression of inflammatory arthritis by apoptotic cells","volume":"186","author":"Notley","year":"2011","journal-title":"J. Immunol."},{"key":"2025022610324982400_r57","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3389\/fimmu.2012.00066","article-title":"Protective roles of natural IgM antibodies","volume":"3","author":"Gr\u00f6nwall","year":"2012","journal-title":"Front. Immunol."},{"key":"2025022610324982400_r58","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.imlet.2009.06.003","article-title":"IgM in microbial infections: taken for granted?","volume":"125","author":"Racine","year":"2009","journal-title":"Immunol. Lett."},{"key":"2025022610324982400_r59","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri2901","article-title":"The double life of a B-1 cell: self-reactivity selects for protective effector functions","volume":"11","author":"Baumgarth","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"2025022610324982400_r60","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1128\/IAI.66.1.361-363.1998","article-title":"Extensive immunoglobulin binding of Plasmodium falciparum-infected erythrocytes in a group of children with moderate anemia","volume":"66","author":"Scholander","year":"1998","journal-title":"Infect. Immun."},{"key":"2025022610324982400_r61","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.it.2006.12.004","article-title":"The many faces of ITAMs","volume":"28","author":"Underhill","year":"2007","journal-title":"Trends Immunol."},{"key":"2025022610324982400_r62","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1093\/jb\/mvp001","article-title":"Protein tyrosine kinase, syk: a key player in phagocytic cells","volume":"145","author":"Tohyama","year":"2009","journal-title":"J. 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Immunol."},{"key":"2025022610324982400_r78","first-page":"296","article-title":"Effects of IL-4 on macrophage functions: increased uptake and killing of a protozoan parasite (Trypanosoma cruzi)","volume":"66","author":"Wirth","year":"1989","journal-title":"Immunology"},{"key":"2025022610324982400_r79","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.4049\/jimmunol.1401026","article-title":"Group V secreted phospholipase A2 is upregulated by IL-4 in human macrophages and mediates phagocytosis via hydrolysis of ethanolamine phospholipids","volume":"194","author":"Rubio","year":"2015","journal-title":"J. Immunol."},{"key":"2025022610324982400_r80","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1038\/s41598-018-38127-9","article-title":"In-depth characterization of monocyte-derived macrophages using a mass cytometry-based phagocytosis assay","volume":"9","author":"Schulz","year":"2019","journal-title":"Sci. Rep."},{"key":"2025022610324982400_r81","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/S0022-2275(20)32377-4","article-title":"Induction of CD36 expression by oxidized LDL and IL-4 by a common signaling pathway dependent on protein kinase C and PPAR-\u03b3","volume":"41","author":"Feng","year":"2000","journal-title":"J. Lipid Res."},{"key":"2025022610324982400_r82","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1097\/01.LAB.0000081392.93701.6F","article-title":"IL-4 receptor signaling is required for mannose receptor expression by macrophages recruited to granulomata but not resident cells in mice infected with Schistosoma mansoni","volume":"83","author":"Linehan","year":"2003","journal-title":"Lab. Invest."},{"key":"2025022610324982400_r83","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1093\/jnen\/nlw081","article-title":"Molecular and cellular responses to interleukin-4 treatment in a rat model of transient ischemia","volume":"75","author":"Lively","year":"2016","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"2025022610324982400_r84","doi-asserted-by":"crossref","first-page":"4050","DOI":"10.1038\/s41598-017-04325-0","article-title":"Cytokines regulate complement receptor immunoglobulin expression and phagocytosis of Candida albicans in human macrophages: a control point in anti-microbial immunity","volume":"7","author":"Munawara","year":"2017","journal-title":"Sci. Rep."},{"key":"2025022610324982400_r85","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1086\/314552","article-title":"Are reactive oxygen species involved in the pathogenesis of murine cerebral malaria?","volume":"179","author":"Sanni","year":"1999","journal-title":"J. Infect. 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