{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T10:51:04Z","timestamp":1774263064852,"version":"3.50.1"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T00:00:00Z","timestamp":1241136000000},"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":[[2009,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mixed parasite infections are common in many parts of the world, but little is known of the effects of concomitant parasite infections on the immune response or severity of clinical disease. We have used the nonlethal malaria infection model of Plasmodium chabaudi AS in combination with the gastrointestinal nematode Heligmosomoides bakeri polygyrus to investigate the impact of nematode infections on malarial morbidity and antimalarial immunity. The data demonstrate that wild-type C57BL\/6 mice coinfected with both parasites simultaneously exhibit a striking increase in mortality, while mice deficient in IFN-\u03b3 or IL-23 survive coinfection. The increase in mortality in wild-type mice was associated with severe liver pathology characterized by extensive coagulative necrosis and an increase in hepatic IFN-\u03b3, IL-17, and IL-22 mRNA expression. This is the first demonstration of increased malaria-associated pathology associated with a switch toward a proinflammatory environment, involving not only IFN-\u03b3 but also the IL-17\/IL-23 axis, as a result of coinfection with a gastrointestinal helminth.<\/jats:p>","DOI":"10.4049\/jimmunol.0803790","type":"journal-article","created":{"date-parts":[[2009,4,21]],"date-time":"2009-04-21T01:07:38Z","timestamp":1240276058000},"page":"5663-5671","source":"Crossref","is-referenced-by-count":36,"title":["Gastrointestinal Nematode Infection Exacerbates Malaria-Induced Liver Pathology"],"prefix":"10.1093","volume":"182","author":[{"given":"Helena","family":"Helmby","sequence":"first","affiliation":[{"name":"Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,5,1]]},"reference":[{"key":"2026012807043330100_R1","first-page":"89","article-title":"Helminth parasites: masters of regulation.","volume-title":"Immunol. Rev.","year":"2004"},{"key":"2026012807043330100_R2","first-page":"51","article-title":"Helminths and the modulation of mucosal inflammation.","volume-title":"Curr. Opin. Gastroenterol.","year":"2005"},{"key":"2026012807043330100_R3","first-page":"386","article-title":"The role of helminth infections in protection from atopic disorders.","volume-title":"Curr. Opin. Allergy Clin. Immunol.","year":"2005"},{"key":"2026012807043330100_R4","first-page":"515","article-title":"Parasitic worms and inflammatory diseases.","volume-title":"Parasite Immunol.","year":"2006"},{"key":"2026012807043330100_R5","first-page":"306","article-title":"IFN-\u03b3- and IL-5-producing cells compartmentalize to different lymphoid organs in Trichinella spiralis-infected mice.","volume-title":"J. Immunol.","year":"1991"},{"key":"2026012807043330100_R6","first-page":"3434","article-title":"A primary intestinal helminthic infection rapidly induces a gut-associated elevation of Th2-associated cytokines and IL-3.","volume-title":"J. Immunol.","year":"1993"},{"key":"2026012807043330100_R7","first-page":"257","article-title":"Early cytokine responses during intestinal parasitic infections.","volume-title":"Immunology","year":"1998"},{"key":"2026012807043330100_R8","first-page":"672","article-title":"The temporal relationship among anti-parasite immune elements expressed during the early phase of infection of the rat with Trichinella spiralis.","volume-title":"Parasitol. Res.","year":"1999"},{"key":"2026012807043330100_R9","first-page":"2553","article-title":"Interleukin-18 regulates intestinal mastocytosis and Th2 cytokine production independently of IFN-\u03b3 during Trichinella spiralis infection.","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012807043330100_R10","first-page":"5167","article-title":"Altered immune responses in mice with concomitant Schistosoma mansoni and Plasmodium chabaudi infection.","volume-title":"Infect. Immun.","year":"1998"},{"key":"2026012807043330100_R11","first-page":"410","article-title":"Malaria-filaria coinfection in mice makes malarial disease more severe unless filarial infection achieves patency.","volume-title":"J. Infect. Dis.","year":"2005"},{"key":"2026012807043330100_R12","first-page":"3531","article-title":"Impairment of protective immunity to blood-stage malaria by concurrent nematode infection.","volume-title":"Infect. Immun.","year":"2005"},{"key":"2026012807043330100_R13","first-page":"359","article-title":"Worms can worsen malaria: towards a new means to roll back malaria?.","volume-title":"Trends Parasitol.","year":"2005"},{"key":"2026012807043330100_R14","first-page":"497","article-title":"Coinfection of helminths and malaria: modulation of the immune responses to malaria.","volume-title":"Parasite Immunol.","year":"2006"},{"key":"2026012807043330100_R15","first-page":"71","article-title":"The response of CD4+ T cells to Plasmodium chabaudi chabaudi.","volume-title":"Immunol. Rev.","year":"1989"},{"key":"2026012807043330100_R16","first-page":"77","article-title":"Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice.","volume-title":"Clin. Exp. Immunol.","year":"1993"},{"key":"2026012807043330100_R17","first-page":"1730","article-title":"A role for B cells in the development of T cell helper function in a malaria infection in mice.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998"},{"key":"2026012807043330100_R18","first-page":"2559","article-title":"Expansion of IL-3-responsive IL-4-producing non-B non-T cells correlates with anemia and IL-3 production in mice infected with blood-stage Plasmodium chabaudi malaria.","volume-title":"Eur. J. Immunol.","year":"1998"},{"key":"2026012807043330100_R19","first-page":"1874","article-title":"Expansion and activation of CD4+CD25+ regulatory T cells in Heligmosomoides polygyrus infection.","volume-title":"Eur. J. Immunol.","year":"2007"},{"key":"2026012807043330100_R20","first-page":"4655","article-title":"Heligmosomoides polygyrus promotes regulatory T-cell cytokine production in the murine normal distal intestine.","volume-title":"Infect. Immun.","year":"2007"},{"key":"2026012807043330100_R21","first-page":"726","article-title":"Heligmosomoides polygyrus induces TLR4 on murine mucosal T cells that produce TGF\u03b2 after lipopolysaccharide stimulation.","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012807043330100_R22","first-page":"536","article-title":"Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces Helicobacter-induced gastric atrophy.","volume-title":"Nat. Med.","year":"2000"},{"key":"2026012807043330100_R23","first-page":"2690","article-title":"Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice.","volume-title":"Eur. J. Immunol.","year":"2004"},{"key":"2026012807043330100_R24","first-page":"5468","article-title":"Concurrent infection with an intestinal helminth parasite impairs host resistance to enteric Citrobacter rodentium and enhances Citrobacter-induced colitis in mice.","volume-title":"Infect. Immun.","year":"2005"},{"key":"2026012807043330100_R25","first-page":"1199","article-title":"Suppression of allergic airway inflammation by helminth-induced regulatory T cells.","volume-title":"J. Exp. Med","year":"2005"},{"key":"2026012807043330100_R26","first-page":"397","article-title":"Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection.","volume-title":"Infect. Immun.","year":"2007"},{"key":"2026012807043330100_R27","first-page":"1628","article-title":"Intestinal helminths protect in a murine model of asthma.","volume-title":"J. Immunol.","year":"2006"},{"key":"2026012807043330100_R28","first-page":"1305","article-title":"Coinfection with Heligmosomoides polygyrus fails to establish CD8+ T-cell immunity against Toxoplasma gondii.","volume-title":"Infect. Immun.","year":"2008"},{"key":"2026012807043330100_R29","first-page":"471","article-title":"IL-12-deficient mice are defective in IFN-\u03b3 production and type 1 cytokine responses.","volume-title":"Immunity","year":"1996"},{"key":"2026012807043330100_R30","first-page":"1397","article-title":"Immune and inflammatory responses in TNF\u03b1-deficient mice: a critical requirement for TNF\u03b1 in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response.","volume-title":"J. Exp. Med","year":"1996"},{"key":"2026012807043330100_R31","first-page":"703","article-title":"Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin.","volume-title":"Science","year":"1994"},{"key":"2026012807043330100_R32","first-page":"1739","article-title":"Multiple defects of immune cell function in mice with disrupted interferon-\u03b3 genes.","volume-title":"Science","year":"1993"},{"key":"2026012807043330100_R33","first-page":"744","article-title":"Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain.","volume-title":"Nature","year":"2003"},{"key":"2026012807043330100_R34","first-page":"263","article-title":"The life cycle of Nematospiroides dubius, Baylis 1926 (Nematoda: Heligmosomidae).","volume-title":"J. Helminthol.","year":"1973"},{"key":"2026012807043330100_R35","first-page":"473","article-title":"Protective immunity to erythrocytic Plasmodium chabaudi AS infection involves IFN\u03b3-mediated responses and a cellular infiltrate to the liver.","volume-title":"Parasitology","year":"2000"},{"key":"2026012807043330100_R36","first-page":"301","article-title":"Essential role of extrathymic T cells in protection against malaria.","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012807043330100_R37","first-page":"4674","article-title":"The role of IL-18 in blood-stage immunity against murine malaria Plasmodium yoelii 265 and Plasmodium berghei ANKA.","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012807043330100_R38","first-page":"972","article-title":"CTLA-4-dependent mechanisms prevent T cell induced-liver pathology during the erythrocyte stage of Plasmodium berghei malaria.","volume-title":"Eur. J. Immunol.","year":"2004"},{"key":"2026012807043330100_R39","first-page":"436","article-title":"Testosterone suppresses protective responses of the liver to blood-stage malaria.","volume-title":"Infect. Immun.","year":"2005"},{"key":"2026012807043330100_R40","first-page":"946","article-title":"The role of lipopolysaccharide-binding protein in modulating the innate immune response.","volume-title":"Microbes Infect.","year":"2006"},{"key":"2026012807043330100_R41","first-page":"221","article-title":"Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation.","volume-title":"Annu. Rev. Immunol.","year":"2007"},{"key":"2026012807043330100_R42","first-page":"4399","article-title":"Central role of endogenous \u03b3 interferon in protective immunity against blood-stage Plasmodium chabaudi AS infection.","volume-title":"Infect. Immun.","year":"2000"},{"key":"2026012807043330100_R43","first-page":"1348","article-title":"IL-12 is required for antibody-mediated protective immunity against blood-stage Plasmodium chabaudi AS malaria infection in mice.","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012807043330100_R44","first-page":"153","article-title":"Lymphotoxin \u03b1 and tumour necrosis factor are not required for control of parasite growth, but differentially regulate cytokine production during Plasmodium chabaudi chabaudi AS infection.","volume-title":"Parasite Immunol.","year":"2007"},{"key":"2026012807043330100_R45","first-page":"39","article-title":"Transforming growth factor \u03b2 production is inversely correlated with severity of murine malaria infection.","volume-title":"J. Exp. Med","year":"1998"},{"key":"2026012807043330100_R46","first-page":"4435","article-title":"A defect in interleukin-10 leads to enhanced malarial disease in Plasmodium chabaudi chabaudi infection in mice.","volume-title":"Infect. Immun.","year":"1999"},{"key":"2026012807043330100_R47","first-page":"4850","article-title":"Pathology of Plasmodium chabaudi chabaudi infection and mortality in interleukin-10-deficient mice are ameliorated by anti-tumor necrosis factor \u03b1 and exacerbated by anti-transforming growth factor \u03b2 antibodies.","volume-title":"Infect. Immun.","year":"2003"},{"key":"2026012807043330100_R48","first-page":"421","article-title":"The role of the liver in immunity to blood-stage murine malaria.","volume-title":"Immunology","year":"1980"},{"key":"2026012807043330100_R49","first-page":"425","article-title":"Differential interleukin-10 expression in interferon regulatory factor-1 deficient mice during Plasmodium berghei blood-stage infection.","volume-title":"Parasite Immunol.","year":"2000"},{"key":"2026012807043330100_R50","first-page":"787","article-title":"Contribution of CD1d-unrestricted hepatic DX5+ NKT cells to liver injury in Plasmodium berghei-parasitized erythrocyte-injected mice.","volume-title":"Int. Immunol.","year":"2004"},{"key":"2026012807043330100_R51","first-page":"2271","article-title":"Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides.","volume-title":"J. Exp. Med","year":"2006"},{"key":"2026012807043330100_R52","first-page":"648","article-title":"Interleukin-22, a TH17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis.","volume-title":"Nature","year":"2007"},{"key":"2026012807043330100_R53","first-page":"647","article-title":"Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation.","volume-title":"Immunity","year":"2007"},{"key":"2026012807043330100_R54","first-page":"333","article-title":"Down-regulation of murine susceptibility to cerebral malaria by inoculation with third-stage larvae of the filarial nematode Brugia pahangi.","volume-title":"Parasitology","year":"1997"},{"key":"2026012807043330100_R55","first-page":"1117","article-title":"Schistosoma mansoni infection cancels the susceptibility to Plasmodium chabaudi through induction of type 1 immune responses in A\/J mice.","volume-title":"Int. Immunol.","year":"2000"},{"key":"2026012807043330100_R56","first-page":"161","article-title":"Increased parasitaemia and delayed parasite clearance in Schistosoma mansoni and Plasmodium berghei co-infected mice.","volume-title":"Acta Trop.","year":"2004"},{"key":"2026012807043330100_R57","first-page":"916","article-title":"Concurrent gastro-intestinal nematode infection does not alter the development of experimental cerebral malaria.","volume-title":"Microbes Infect.","year":"2008"},{"key":"2026012807043330100_R58","first-page":"272","article-title":"Counter-regulatory anti-parasite cytokine responses during concurrent Plasmodium yoelii and intestinal helminth infections in mice.","volume-title":"Exp. Parasitol.","year":"2008"},{"key":"2026012807043330100_R59","first-page":"69","article-title":"The tissue reactions of mice to infection with Heligmosomoides polygyrus.","volume-title":"J. Helminthol.","year":"1988"},{"key":"2026012807043330100_R60","first-page":"2424","article-title":"Peripheral CD4 T cells rapidly accumulate at the host: parasite interface during an inflammatory Th2 memory response.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012807043330100_R61","first-page":"325","article-title":"Stage-specific antigens of Nematospiroides dubius.","volume-title":"Immunology","year":"1984"},{"key":"2026012807043330100_R62","first-page":"1164","article-title":"Stage-specific antigens of Nematospiroides dubius Baylis, 1926 (Nematoda: Heligmosomides).","volume-title":"J. Parasitol.","year":"1987"},{"key":"2026012807043330100_R63","first-page":"232","article-title":"Heligmosomoides polygyrus: retarded development and stunting of larvae by antibodies specific for excretory\/secretory antigens.","volume-title":"Exp. Parasitol.","year":"1988"},{"key":"2026012807043330100_R64","first-page":"495","article-title":"Immunosuppressive proteins secreted by the gastrointestinal nematode parasite Heligmosomoides polygyrus.","volume-title":"Int. J. Parasitol.","year":"1994"},{"key":"2026012807043330100_R65","first-page":"601","article-title":"Heligmosomoides polygyrus immunomodulatory factor (IMF), targets T-lymphocytes.","volume-title":"Parasite Immunol.","year":"1998"},{"key":"2026012807043330100_R66","first-page":"955","article-title":"Memory TH2 cells induce alternatively activated macrophages to mediate protection against nematode parasites.","volume-title":"Nat. Med.","year":"2006"},{"key":"2026012807043330100_R67","first-page":"5921","article-title":"Cutting edge: the acquisition of TLR tolerance during malaria infection impacts T cell activation.","volume-title":"J. Immunol.","year":"2005"},{"key":"2026012807043330100_R68","first-page":"19","article-title":"Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin.","volume-title":"J. Exp. Med.","year":"2005"},{"key":"2026012807043330100_R69","first-page":"5928","article-title":"Plasmodium berghei infection in mice induces liver injury by an IL-12- and Toll-like receptor\/myeloid differentiation factor 88-dependent mechanism.","volume-title":"J. Immunol.","year":"2001"},{"key":"2026012807043330100_R70","first-page":"2383","article-title":"IL-10 is critical for host resistance and survival during gastrointestinal helminth infection.","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012807043330100_R71","first-page":"623","article-title":"Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology.","volume-title":"Immunity","year":"2004"},{"key":"2026012807043330100_R72","first-page":"367","article-title":"Age-dependent characteristics of protection v. susceptibility to Plasmodium falciparum.","volume-title":"Ann. Trop. Med. Parasitol.","year":"1998"},{"key":"2026012807043330100_R73","first-page":"51","volume-title":"Deworming for health and development. Report of the third global meeting of the partners for parasite control","year":"2005"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/9\/5663\/62685294\/8913.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/9\/5663\/62685294\/8913.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:04:55Z","timestamp":1769601895000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/182\/9\/5663\/8007686"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,5,1]]},"references-count":73,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2009,5,1]]},"published-print":{"date-parts":[[2009,5,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0803790","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,5]]},"published":{"date-parts":[[2009,5,1]]}}}