{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T22:13:19Z","timestamp":1789855999650,"version":"4.0.1"},"reference-count":87,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2010,3,1]],"date-time":"2010-03-01T00:00:00Z","timestamp":1267401600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The postgenomic era has revolutionized approaches to defining host-pathogen interactions and the investigation of the influence of genetic variation in either protagonist upon infection outcome. We analyzed pathology induced by infection with two genetically distinct<jats:italic>Trypanosoma brucei<\/jats:italic>strains and found that pathogenesis is partly strain specific, involving distinct host mechanisms. Infections of BALB\/c mice with one strain (927) resulted in more severe anemia and greater erythropoietin production compared to infections with the second strain (247), which, contrastingly, produced greater splenomegaly and reticulocytosis. Plasma interleukin-10 (IL-10) and gamma interferon levels were significantly higher in strain 927-infected mice, whereas IL-12 was higher in strain 247-infected mice. To define mechanisms underlying these differences, expression microarray analysis of host genes in the spleen at day 10 postinfection was undertaken. Rank product analysis (RPA) showed that 40% of the significantly differentially expressed genes were specific to infection with one or the other trypanosome strain. RPA and pathway analysis identified LXR\/RXR signaling, IL-10 signaling, and alternative macrophage activation as the most significantly differentially activated host processes. These data suggest that innate immune response modulation is a key determinant in trypanosome infections, the pattern of which can vary, dependent upon the trypanosome strain. This strongly suggests that a parasite genetic component is responsible for causing disease in the host. Our understanding of trypanosome infections is largely based on studies involving single parasite strains, and our results suggest that an integrated host-parasite approach is required for future studies on trypanosome pathogenesis. Furthermore, it is necessary to incorporate parasite variation into both experimental systems and models of pathogenesis.<\/jats:p>","DOI":"10.1128\/iai.00943-09","type":"journal-article","created":{"date-parts":[[2010,1,20]],"date-time":"2010-01-20T04:52:47Z","timestamp":1263963167000},"page":"1096-1108","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Role for Parasite Genetic Diversity in Differential Host Responses to<i>Trypanosoma brucei<\/i>Infection"],"prefix":"10.1128","volume":"78","author":[{"given":"Liam J.","family":"Morrison","sequence":"first","affiliation":[{"name":"Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"McLellan","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Sweeney","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi N.","family":"Chan","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"MacLeod","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Tait","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Michael R.","family":"Turner","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, University of Glasgow, Biomedical Research Centre, 120 University Place, Glasgow G12 8TA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01185-08"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14694-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.63.4.429"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.9.6168"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2009.06.010"},{"key":"e_1_3_2_7_2","first-page":"220","volume":"110","year":"2007","unstructured":"Boulland, M. L., J. Marquet, V. Molinier-Frenkel, P. Moller, C. Guiter, F. Lasoudris, C. Copie-Bergman, M. Baia, P. Gaulard, K. Leroy, and F. Castellano. 2007. Human IL4I1 is a secreted l-phenylalanine oxidase expressed by mature dendritic cells that inhibits T-lymphocyte proliferation. Blood110:220-227.","journal-title":"Blood"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.07.055"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.6.1861"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.4049\/jimmunol.156.7.2534","volume":"156","year":"1996","unstructured":"Colotta, F., S. Saccani, J. G. Giri, S. K. Dower, J. E. Sims, M. Introna, and A. Mantovani. 1996. Regulated expression and release of the IL-1 decoy receptor in human mononuclear phagocytes. J. Immunol.156:2534-2541.","journal-title":"J. Immunol."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000071514.36428.61"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2006.04.001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.5.1681"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2004.11.008"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000333"},{"key":"e_1_3_2_16_2","first-page":"12","volume":"30","year":"1973","unstructured":"Geigy, R., and M. Kauffmann. 1973. Sleeping sickness survey in the Serengeti area (Tanzania) 1971. I. Examination of large mammals for trypanosomes. Acta Trop.30:12-23.","journal-title":"Acta Trop."},{"key":"e_1_3_2_17_2","first-page":"575","volume":"108","year":"2006","unstructured":"Ghassabeh, G. H., P. de Baetselier, L. Brys, W. No\u00ebl, J. Van Ginderachter, S. Meerschaut, A. Beschin, F. Brombacher, and G. Raes. 2006. Identification of a common gene signature for type II cytokine-associated myeloid cells elicited in vivo in different pathologic conditions. Blood108:575-583.","journal-title":"Blood"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1973.11686861"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.182.2.1107"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.5.2748"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1232392100"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"6775","DOI":"10.4049\/jimmunol.161.12.6775","volume":"161","year":"1998","unstructured":"Hertz, C. J., H. Filutowicz, and J. M. Mansfield. 1998. Resistance to the African trypanosomes is IFN-gamma dependent. J. Immunol.161:6775-6783.","journal-title":"J. Immunol."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1998.1429"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(91)90089-F"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.2.1115"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2007.10.008"},{"key":"e_1_3_2_27_2","first-page":"1582","volume":"105","year":"1975","unstructured":"Huan, C. N., L. Webb, P. H. Lambert, and P. A. Miescher. 1975. Pathogenesis of the anemia in African trypanosomiasis: characterization and purification of a hemolytic factor. Schweiz. Med. Wochenschr.105:1582-1583.","journal-title":"Schweiz. Med. Wochenschr."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/4.2.249"},{"key":"e_1_3_2_29_2","first-page":"13","year":"1985","unstructured":"Jenkins, G. C., and C. A. Facer. 1985. Hematology of African trypanosomiasis, p. 13-44. In I. Tizard (ed.), Immunology and pathogenesis of trypanosomiasis. Academic Press, Inc., New York, NY.","journal-title":"Immunology and pathogenesis of trypanosomiasis"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2007.08.007"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.09.032"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm820"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0697-194"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052155999"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364345"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(70)90120-7"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-7-295"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.4.1563-1566.1995"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.12.7040-7044.2004"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1086\/522011"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki980"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.6.3128-3132.1999"},{"key":"e_1_3_2_43_2","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.4049\/jimmunol.160.4.1949","volume":"160","year":"1998","unstructured":"Magez, S., B. Stijlemans, M. Radwanska, E. Pays, M. A. Ferguson, and P. De Baetselier. 1998. The glycosyl-inositol-phosphate and dimyristoylglycerol moieties of the glycosylphosphatidylinositol anchor of the trypanosome variant-specific surface glycoprotein are distinct macrophage-activating factors. J. Immunol.160:1949-1956.","journal-title":"J. Immunol."},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1086\/381151"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605237200"},{"key":"e_1_3_2_46_2","first-page":"97","volume":"3","year":"2004","unstructured":"McDevitt, M. A., J. Xie, V. Gordeuk, and R. Bucala. 2004. The anemia of malaria infection: role of inflammatory cytokines. Curr. Hematol. Rep.3:97-106.","journal-title":"Curr. Hematol. Rep."},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2009.01383.x"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000557"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(79)90121-8"},{"key":"e_1_3_2_50_2","first-page":"25","volume":"32","year":"1978","unstructured":"Morrison, W. I., G. E. Roelants, K. S. Mayor-Withey, and M. Murray. 1978. Susceptibility of inbred strains of mice to Trypanosoma congolense: correlation with changes in spleen lymphocyte populations. Clin. Exp. Immunol.32:25-40.","journal-title":"Clin. Exp. Immunol."},{"key":"e_1_3_2_51_2","first-page":"503","volume":"109","year":"1981","unstructured":"Murray, M., D. J. Clifford, G. Gettinby, W. F. Snow, and W. I. McIntyre. 1981. Susceptibility to African trypanosomiasis of N\u2032Dama and Zebu cattle in an area of Glossina morsitans submorsitans challenge. Vet. Rec.109:503-510.","journal-title":"Vet. Rec."},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-308X(08)60274-2"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2006.02.012"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2004.02717.x"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4017(02)00360-6"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-003-0844-3"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.71.313"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1086\/320731"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.11.6180-6187.2002"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005170"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-207"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00100.2006"},{"key":"e_1_3_2_63_2","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.4049\/jimmunol.157.5.2058","volume":"157","year":"1996","unstructured":"Ohmori, Y., M. F. Smith, Jr., and T. A. Hamilton. 1996. IL-4-induced expression of the IL-1 receptor antagonist gene is mediated by STAT6. J. Immunol.157:2058-2065.","journal-title":"J. Immunol."},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.2307\/3276780"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.1991.tb00294.x"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000078"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.05.007"},{"key":"e_1_3_2_68_2","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1189\/jlb.71.4.597","volume":"71","year":"2002","unstructured":"Raes, G., P. De Baetselier, W. No\u00ebl, A. Beschin, F. Brombacher, and G. Hassanzadeh Gh. 2002. Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages. J. Leukoc. Biol.71:597-602.","journal-title":"J. Leukoc. Biol."},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1080\/1044667031000137629"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.2.801"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1133690"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-7-3"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1086\/382596"},{"key":"e_1_3_2_74_2","first-page":"369","year":"2004","unstructured":"Shaw, A. P. M. 2004. Economics of African trypanosomiasis, p. 369-402. In I. Maudlin, P. H. Holmes, and M. A. Miles (ed.), The trypanosomiases. CABI Publishing, Wallingford, United Kingdom.","journal-title":"The trypanosomiases"},{"key":"e_1_3_2_75_2","unstructured":"Nonparametric statistics for the behavioural sciences. 1988"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.17.7907"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2007.05.005"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2008.07.023"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.172117099"},{"key":"e_1_3_2_80_2","first-page":"273","volume":"67","year":"2000","unstructured":"Taiwo, V. O., and V. O. Anosa. 2000. In vitro erythrophagocytosis by cultured macrophages stimulated with extraneous substances and those isolated from the blood, spleen and bone marrow of Boran and N\u2032Dama cattle infected with Trypanosoma congolense and Trypanosoma vivax. Onderstepoort J. Vet. Res.67:273-287.","journal-title":"Onderstepoort J. Vet. Res."},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1133643"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182000081841"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407749101"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-165X.2002.tb00284.x"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4017(00)00430-1"},{"key":"e_1_3_2_86_2","first-page":"71","volume":"81","year":"2006","unstructured":"World Health Organization. 2006. Human African trypanosomiasis (sleeping sickness): epidemiological update. Wkly. Epidemiol. Rec.81:71-80.","journal-title":"Wkly. Epidemiol. Rec."},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2006.11.007"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.2.695"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00943-09","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00943-09","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T17:36:42Z","timestamp":1685381802000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00943-09"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3]]},"references-count":87,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2010,3]]}},"alternative-id":["10.1128\/IAI.00943-09"],"URL":"https:\/\/doi.org\/10.1128\/iai.00943-09","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3]]},"assertion":[{"value":"2009-08-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-01-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}