{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:53:13Z","timestamp":1790524393027,"version":"4.1.0"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2010,3,30]],"date-time":"2010-03-30T00:00:00Z","timestamp":1269907200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0000648","type":"journal-article","created":{"date-parts":[[2010,3,29]],"date-time":"2010-03-29T21:39:47Z","timestamp":1269898787000},"page":"e648","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":89,"title":["Delineation of Diverse Macrophage Activation Programs in Response to Intracellular Parasites and Cytokines"],"prefix":"10.1371","volume":"4","author":[{"given":"Shuyi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles C.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajeev","family":"Batra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"McKerrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P'ng","family":"Loke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2010,3,30]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1189\/jlb.0602325","article-title":"The many faces of macrophage activation.","volume":"73","author":"DM Mosser","year":"2003","journal-title":"J Leukoc Biol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1146\/annurev.iy.02.040184.001435","article-title":"The cell biology of macrophage activation.","volume":"2","author":"DO Adams","year":"1984","journal-title":"Annu Rev Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.immunol.20.083001.084359","article-title":"Innate immune recognition.","volume":"20","author":"CA Janeway Jr","year":"2002","journal-title":"Annu Rev Immunol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1146\/annurev.immunol.18.1.275","article-title":"CD8+ T cell effector mechanisms in resistance to infection.","volume":"18","author":"JT Harty","year":"2000","journal-title":"Annu Rev Immunol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nri978","article-title":"Alternative activation of macrophages.","volume":"3","author":"S Gordon","year":"2003","journal-title":"Nat Rev Immunol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.4049\/jimmunol.147.11.3815","article-title":"IL-10 inhibits cytokine production by activated macrophages.","volume":"147","author":"DF Fiorentino","year":"1991","journal-title":"J Immunol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1172\/JCI1112","article-title":"Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine\/paracrine mechanisms involving TGF-beta, PGE2, and PAF.","volume":"101","author":"VA Fadok","year":"1998","journal-title":"J Clin Invest"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.immuni.2005.10.001","article-title":"Macrophage polarization comes of age.","volume":"23","author":"A Mantovani","year":"2005","journal-title":"Immunity"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1073\/pnas.022649799","article-title":"Human macrophage activation programs induced by bacterial pathogens.","volume":"99","author":"GJ Nau","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"11386","DOI":"10.1073\/pnas.0403215101","article-title":"A specific gene expression program triggered by Gram-positive bacteria in the cytosol.","volume":"101","author":"RL McCaffrey","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"15623","DOI":"10.1073\/pnas.95.26.15623","article-title":"Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays.","volume":"95","author":"SD Der","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s00436-007-0819-x","article-title":"Transcriptome profile of Trypanosoma cruzi-infected cells: simultaneous up- and down-regulation of proliferation inhibitors and promoters.","volume":"102","author":"T Shigihara","year":"2008","journal-title":"Parasitol Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/1471-2164-10-119","article-title":"Transcriptional signatures of BALB\/c mouse macrophages housing multiplying Leishmania amazonensis amastigotes.","volume":"10","author":"J Osorio y Fortea","year":"2009","journal-title":"BMC Genomics"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1128\/IAI.01320-07","article-title":"Comparison of the effects of Leishmania major or Leishmania donovani infection on macrophage gene expression.","volume":"76","author":"DJ Gregory","year":"2008","journal-title":"Infect Immun"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"5625","DOI":"10.1093\/nar\/gkm623","article-title":"A systematic strategy for large-scale analysis of genotype phenotype correlations: identification of candidate genes involved in African trypanosomiasis.","volume":"35","author":"P Fisher","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"e252","DOI":"10.1371\/journal.pntd.0000252","article-title":"Macrophage and T-Cell Gene Expression in a Model of Early Infection with the Protozoan Leishmania chagasi.","volume":"2","author":"NA Ettinger","year":"2008","journal-title":"PLoS Negl Trop Dis"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1186\/1471-2164-10-252","article-title":"Cytokine-dependent and-independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling.","volume":"10","author":"JA Costales","year":"2009","journal-title":"BMC Genomics"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.4049\/jimmunol.166.5.3416","article-title":"General suppression of macrophage gene expression during Leishmania donovani infection.","volume":"166","author":"S Buates","year":"2001","journal-title":"J Immunol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1182\/blood-2002-10-3232","article-title":"Unique gene expression profiles of human macrophages and dendritic cells to phylogenetically distinct parasites.","volume":"102","author":"D Chaussabel","year":"2003","journal-title":"Blood"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1128\/IAI.72.4.2111-2122.2004","article-title":"Novel program of macrophage gene expression induced by phagocytosis of Leishmania chagasi.","volume":"72","author":"NE Rodriguez","year":"2004","journal-title":"Infect Immun"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1074\/jbc.M109037200","article-title":"Immediate\/early response to Trypanosoma cruzi infection involves minimal modulation of host cell transcription.","volume":"277","author":"S Vaena de Avalos","year":"2002","journal-title":"J Biol Chem"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.4049\/jimmunol.0800621","article-title":"Trypanosoma cruzi triggers an early type I IFN response in vivo at the site of intradermal infection.","volume":"182","author":"AD Chessler","year":"2009","journal-title":"J Immunol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"12289","DOI":"10.1073\/pnas.1635231100","article-title":"Protective immunity against Helicobacter is characterized by a unique transcriptional signature.","volume":"100","author":"A Mueller","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/41131","article-title":"A human homologue of the Drosophila Toll protein signals activation of adaptive immunity.","volume":"388","author":"R Medzhitov","year":"1997","journal-title":"Nature"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/nri1004","article-title":"Innate immune sensing and its roots: the story of endotoxin.","volume":"3","author":"B Beutler","year":"2003","journal-title":"Nat Rev Immunol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1002\/1521-4141(200103)31:3<876::AID-IMMU876>3.0.CO;2-I","article-title":"Silent infection of bone marrow-derived dendritic cells by Leishmania mexicana amastigotes.","volume":"31","author":"CL Bennett","year":"2001","journal-title":"Eur J Immunol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"7059","DOI":"10.4049\/jimmunol.177.10.7059","article-title":"TLR-dependent induction of IFN-beta mediates host defense against Trypanosoma cruzi.","volume":"177","author":"R Koga","year":"2006","journal-title":"J Immunol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.coi.2007.06.003","article-title":"Immune system recognition of Trypanosoma cruzi.","volume":"19","author":"RL Tarleton","year":"2007","journal-title":"Curr Opin Immunol"},{"key":"ref29","first-page":"222","article-title":"Immunology of African trypanosomiasis;","author":"JM Mansfield","year":"1990"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.4049\/jimmunol.150.7.2910","article-title":"Characterization of T helper cell responses to the trypanosome variant surface glycoprotein.","volume":"150","author":"KW Schleifer","year":"1993","journal-title":"J Immunol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1189\/jlb.69.5.685","article-title":"Analysis of macrophage activation in African trypanosomiasis.","volume":"69","author":"DM Paulnock","year":"2001","journal-title":"J Leukoc Biol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/nature05894","article-title":"Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance.","volume":"447","author":"JI Odegaard","year":"2007","journal-title":"Nature"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.4049\/jimmunol.169.5.2253","article-title":"Shaping gene expression in activated and resting primary macrophages by IL-10.","volume":"169","author":"R Lang","year":"2002","journal-title":"J Immunol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1172\/JCI27727","article-title":"The IL-21 receptor augments Th2 effector function and alternative macrophage activation.","volume":"116","author":"J Pesce","year":"2006","journal-title":"J Clin Invest"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S1359-6101(03)00022-4","article-title":"Biological functions of tumor necrosis factor cytokines and their receptors.","volume":"14","author":"K Pfeffer","year":"2003","journal-title":"Cytokine Growth Factor Rev"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"4220","DOI":"10.4049\/jimmunol.164.8.4220","article-title":"Type I IFN modulates innate and specific antiviral immunity.","volume":"164","author":"JE Durbin","year":"2000","journal-title":"J Immunol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1126\/science.1496401","article-title":"Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor.","volume":"257","author":"C Schindler","year":"1992","journal-title":"Science"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/366583a0","article-title":"Interferon-induced nuclear signalling by Jak protein tyrosine kinases.","volume":"366","author":"O Silvennoinen","year":"1993","journal-title":"Nature"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S1359-6101(03)00021-2","article-title":"The signaling adaptors and pathways activated by TNF superfamily.","volume":"14","author":"PW Dempsey","year":"2003","journal-title":"Cytokine Growth Factor Rev"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0092-8674(00)80984-8","article-title":"TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways.","volume":"84","author":"H Hsu","year":"1996","journal-title":"Cell"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1084\/jem.191.7.1233","article-title":"Requirement of tumor necrosis factor receptor-associated factor (TRAF)6 in interleukin 17 signal transduction.","volume":"191","author":"R Schwandner","year":"2000","journal-title":"J Exp Med"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/ni0307-232","article-title":"Act1-ivating IL-17 inflammation.","volume":"8","author":"CA Hunter","year":"2007","journal-title":"Nat Immunol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"24138","DOI":"10.1074\/jbc.M604597200","article-title":"Identification of common transcriptional regulatory elements in interleukin-17 target genes.","volume":"281","author":"F Shen","year":"2006","journal-title":"J Biol Chem"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/ni1576","article-title":"TNF activates an IRF1-dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon-response genes.","volume":"9","author":"A Yarilina","year":"2008","journal-title":"Nat Immunol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1189\/jlb.0406249","article-title":"Biochemical and functional characterization of three activated macrophage populations.","volume":"80","author":"JP Edwards","year":"2006","journal-title":"J Leukoc Biol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"813","DOI":"10.4049\/jimmunol.121.3.813","article-title":"Activation of mononuclear phagocytes: fact, fancy, and future.","volume":"121","author":"ZA Cohn","year":"1978","journal-title":"J Immunol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrmicro1126","article-title":"Insights into host responses against pathogens from transcriptional profiling.","volume":"3","author":"RG Jenner","year":"2005","journal-title":"Nat Rev Microbiol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"7917","DOI":"10.4049\/jimmunol.181.11.7917","article-title":"A novel IFN regulatory factor 3-dependent pathway activated by trypanosomes triggers IFN-beta in macrophages and fibroblasts.","volume":"181","author":"AD Chessler","year":"2008","journal-title":"J Immunol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1242\/jcs.112.18.2993","article-title":"Leishmania species: models of intracellular parasitism.","volume":"112 Pt 18","author":"J Alexander","year":"1999","journal-title":"J Cell Sci"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/00062752-200001000-00006","article-title":"Leishmania parasites and their ploys to disrupt macrophage activation.","volume":"7","author":"MM Kane","year":"2000","journal-title":"Curr Opin Hematol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.4049\/jimmunol.173.5.3297","article-title":"Inhibition of lipopolysaccharide-induced macrophage IL-12 production by Leishmania mexicana amastigotes: the role of cysteine peptidases and the NF-kappaB signaling pathway.","volume":"173","author":"P Cameron","year":"2004","journal-title":"J Immunol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1002\/(SICI)1521-4141(199808)28:08<2467::AID-IMMU2467>3.0.CO;2-1","article-title":"Phagocytosis of Leishmania mexicana amastigotes by macrophages leads to a sustained suppression of IL-12 production.","volume":"28","author":"N Weinheber","year":"1998","journal-title":"Eur J Immunol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.4049\/jimmunol.171.7.3711","article-title":"Cysteine protease B of Leishmania mexicana inhibits host Th1 responses and protective immunity.","volume":"171","author":"LU Buxbaum","year":"2003","journal-title":"J Immunol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/1521-4141(200204)32:4<1003::AID-IMMU1003>3.0.CO;2-P","article-title":"Cruzipain, a major Trypanosoma cruzi antigen, conditions the host immune response in favor of parasite.","volume":"32","author":"L Giordanengo","year":"2002","journal-title":"Eur J Immunol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1189\/jlb.72.4.727","article-title":"Alternative activation and increase of Trypanosoma cruzi survival in murine macrophages stimulated by cruzipain, a parasite antigen.","volume":"72","author":"C Stempin","year":"2002","journal-title":"J Leukoc Biol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/eji.200324313","article-title":"Arginase induction promotes Trypanosoma cruzi intracellular replication in Cruzipain-treated J774 cells through the activation of multiple signaling pathways.","volume":"34","author":"CC Stempin","year":"2004","journal-title":"Eur J Immunol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1128\/IAI.73.4.2101-2108.2005","article-title":"Interleukin 10- and Fcgamma receptor-deficient mice resolve Leishmania mexicana lesions.","volume":"73","author":"LU Buxbaum","year":"2005","journal-title":"Infect Immun"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1128\/IAI.70.4.2151-2158.2002","article-title":"Early enhanced Th1 response after Leishmania amazonensis infection of C57BL\/6 interleukin-10-deficient mice does not lead to resolution of infection.","volume":"70","author":"DE Jones","year":"2002","journal-title":"Infect Immun"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.4049\/jimmunol.166.2.1141","article-title":"The role of IL-10 in promoting disease progression in leishmaniasis.","volume":"166","author":"MM Kane","year":"2001","journal-title":"J Immunol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2172-3-7","article-title":"IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype.","volume":"3","author":"P Loke","year":"2002","journal-title":"BMC Immunol"}],"container-title":["PLoS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0000648","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T10:45:42Z","timestamp":1685529942000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0000648"}},"subtitle":[],"editor":[{"given":"Judith E.","family":"Allen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2010,3,30]]},"references-count":60,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2010,3,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0000648","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,30]]}}}