{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T01:13:24Z","timestamp":1774574004940,"version":"3.50.1"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T00:00:00Z","timestamp":1384992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1003334","type":"journal-article","created":{"date-parts":[[2013,11,21]],"date-time":"2013-11-21T22:18:56Z","timestamp":1385072336000},"page":"e1003334","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["A Petri Net Model of Granulomatous Inflammation: Implications for IL-10 Mediated Control of Leishmania donovani Infection"],"prefix":"10.1371","volume":"9","author":[{"given":"Luca","family":"Albergante","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon","family":"Timmis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynette","family":"Beattie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul M.","family":"Kaye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2013,11,21]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.cimid.2004.03.004","article-title":"Leishmaniasis: current situation and new perspectives","volume":"27","author":"P Desjeux","year":"2004","journal-title":"Comp Immunol Microbiol Infect Dis"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"e35671","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence","volume":"7","author":"J Alvar","year":"2012","journal-title":"PLoS One"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1111\/j.1469-0691.2011.03610.x","article-title":"Visceral leishmaniasis: immunology and prospects for a vaccine","volume":"17","author":"PM Kaye","year":"2011","journal-title":"Clin Microbiol Infect"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.0105-2896.2004.00188.x","article-title":"The immunopathology of experimental visceral leishmaniasis","volume":"201","author":"PM Kaye","year":"2004","journal-title":"Immunol Rev"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1046\/j.1365-2613.2001.00199.x","article-title":"Tissue granuloma structure-function in experimental visceral leishmaniasis","volume":"82","author":"HW Murray","year":"2001","journal-title":"Int J Exp Pathol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/0035-9203(74)90067-4","article-title":"Studies on Mediterranean leishmaniasis. 2. Asymptomatic cases of visceral leishmaniasis","volume":"68","author":"S Pampiglione","year":"1974","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"618","DOI":"10.4269\/ajtmh.2004.70.618","article-title":"Organ-specific immunity in canine visceral leishmaniasis: analysis of symptomatic and asymptomatic dogs naturally infected with Leishmania chagasi","volume":"70","author":"MA Sanchez","year":"2004","journal-title":"Am J Trop Med Hyg"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"S316","DOI":"10.1093\/infdis\/jis043","article-title":"Local immune responses in human tuberculosis: learning from the site of infection","volume":"205 Suppl 2","author":"S Brighenti","year":"2012","journal-title":"J Infect Dis"},{"key":"ref9","first-page":"464","article-title":"Granulomatous lung disease","volume":"102","author":"A Cancellieri","year":"2010","journal-title":"Pathologica"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/nri3211","article-title":"Revisiting the role of the granuloma in tuberculosis","volume":"12","author":"L Ramakrishnan","year":"2012","journal-title":"Nat Rev Immunol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.autrev.2010.02.006","article-title":"Wegener&apos;s Granulomatosis vasculitis and granuloma","volume":"9","author":"AM Schilder","year":"2010","journal-title":"Autoimmun Rev"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fimmu.2013.00035","article-title":"Functional complexity of the Leishmania granuloma and the potential of in silico modeling","volume":"4","author":"JW Moore","year":"2013","journal-title":"Front Immunol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e10107","DOI":"10.1371\/journal.pone.0010107","article-title":"Quantification of parasite load in clinical samples of leishmaniasis patients: IL-10 level correlates with parasite load in visceral leishmaniasis","volume":"5","author":"S Verma","year":"2010","journal-title":"PLoS One"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1574-695X.2012.00931.x","article-title":"Recent insights into microbial triggers of interleukin-10 production in the host and the impact on infectious disease pathogenesis","volume":"64","author":"BL Duell","year":"2012","journal-title":"FEMS Immunol Med Microbiol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nri2711","article-title":"The regulation of IL-10 production by immune cells","volume":"10","author":"M Saraiva","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.4049\/jimmunol.148.6.1792","article-title":"IL-10 inhibits parasite killing and nitrogen oxide production by IFN-gamma-activated macrophages","volume":"148","author":"RT Gazzinelli","year":"1992","journal-title":"J Immunol"},{"key":"ref17","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":"ref18","doi-asserted-by":"crossref","first-page":"469","DOI":"10.4049\/jimmunol.175.1.469","article-title":"ERK activation following macrophage FcgammaR ligation leads to chromatin modifications at the IL-10 locus","volume":"175","author":"M Lucas","year":"2005","journal-title":"J Immunol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"3444","DOI":"10.4049\/jimmunol.146.10.3444","article-title":"IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells","volume":"146","author":"DF Fiorentino","year":"1991","journal-title":"J Immunol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"e1002827","DOI":"10.1371\/journal.ppat.1002827","article-title":"IL-10-producing Th1 cells and disease progression are regulated by distinct CD11c(+) cell populations during visceral leishmaniasis","volume":"8","author":"BM Owens","year":"2012","journal-title":"PLoS Pathog"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.immuni.2004.10.012","article-title":"Stromal cells direct local differentiation of regulatory dendritic cells","volume":"21","author":"M Svensson","year":"2004","journal-title":"Immunity"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"4090","DOI":"10.4049\/jimmunol.180.6.4090","article-title":"IL-10 and TGF-beta control the establishment of persistent and transmissible infections produced by Leishmania tropica in C57BL\/6 mice","volume":"180","author":"CF Anderson","year":"2008","journal-title":"J Immunol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.4049\/jimmunol.1003588","article-title":"IL-27 and IL-21 are associated with T cell IL-10 responses in human visceral leishmaniasis","volume":"186","author":"NA Ansari","year":"2011","journal-title":"J Immunol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1084\/jem.194.10.1497","article-title":"The role of interleukin (IL)-10 in the persistence of Leishmania major in the skin after healing and the therapeutic potential of anti-IL-10 receptor antibody for sterile cure","volume":"194","author":"Y Belkaid","year":"2001","journal-title":"J Exp Med"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1093\/infdis\/jir461","article-title":"IL-10 neutralization promotes parasite clearance in splenic aspirate cells from patients with visceral leishmaniasis","volume":"204","author":"S Gautam","year":"2011","journal-title":"J Infect Dis"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1084\/jem.20061141","article-title":"Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis","volume":"204","author":"S Nylen","year":"2007","journal-title":"J Exp Med"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"17123","DOI":"10.1073\/pnas.0904955106","article-title":"A human IL10 BAC transgene reveals tissue-specific control of IL-10 expression and alters disease outcome","volume":"106","author":"D Ranatunga","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1002\/eji.200635937","article-title":"Distinct roles for IL-6 and IL-12p40 in mediating protection against Leishmania donovani and the expansion of IL-10+ CD4+ T cells","volume":"36","author":"S Stager","year":"2006","journal-title":"Eur J Immunol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.immuni.2008.06.012","article-title":"Posttranscriptional regulation of II10 gene expression allows natural killer cells to express immunoregulatory function","volume":"29","author":"A Maroof","year":"2008","journal-title":"Immunity"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/j.1600-065X.2008.00635.x","article-title":"Strategies for use of IL-10 or its antagonists in human disease","volume":"223","author":"A O'Garra","year":"2008","journal-title":"Immunol Rev"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1128\/IAI.01011-07","article-title":"Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungs","volume":"76","author":"SD Chakravarty","year":"2008","journal-title":"Infect Immun"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"535","DOI":"10.3934\/mbe.2005.2.535","article-title":"A metapopulation model of granuloma formation in the lung during infection with mycobacterium tuberculosis","volume":"2","author":"S Ganguli","year":"2005","journal-title":"Math Biosci Eng"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.jtbi.2010.05.012","article-title":"TNF and IL-10 are major factors in modulation of the phagocytic cell environment in lung and lymph node in tuberculosis: a next-generation two-compartmental model","volume":"265","author":"S Marino","year":"2010","journal-title":"J Theor Biol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.4049\/jimmunol.0802297","article-title":"Synergy between individual TNF-dependent functions determines granuloma performance for controlling Mycobacterium tuberculosis infection","volume":"182","author":"JC Ray","year":"2009","journal-title":"J Immunol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jtbi.2008.01.010","article-title":"The timing of TNF and IFN-gamma signaling affects macrophage activation strategies during Mycobacterium tuberculosis infection","volume":"252","author":"JC Ray","year":"2008","journal-title":"J Theor Biol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"e19544","DOI":"10.1371\/journal.pone.0019544","article-title":"An in silico modeling approach to understanding the dynamics of sarcoidosis","volume":"6","author":"BD Aguda","year":"2011","journal-title":"PLoS One"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Flugge AJ, Timmis J, Beattie L, Kaye PM (2009) Modeling and simulation of granuloma formation in visceral leishmaniasis. IEEE Congress on Evolutionary Computation Trondheim, Norway.","DOI":"10.1109\/CEC.2009.4983329"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"790482","DOI":"10.1155\/2012\/790482","article-title":"Modeling innate immune response to early Mycobacterium infection","volume":"2012","author":"RV Carvalho","year":"2012","journal-title":"Comput Math Methods Med"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Koch I, Reisig W, Screiber F (2011) Modeling in Systems Biology: The Petri Net Approach. pp. 364.","DOI":"10.1007\/978-1-84996-474-6"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e34143","DOI":"10.1371\/journal.pone.0034143","article-title":"B cell: T cell interactions occur within hepatic granulomas during experimental visceral leishmaniasis","volume":"7","author":"JW Moore","year":"2012","journal-title":"PLoS One"},{"key":"ref41","unstructured":"Mood A, Graybill F, Boes D (1974) Introduction to the Theory of Statistics. London: McGraw Hill Higher Education. 480 p."},{"key":"ref42","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.1128\/IAI.00422-06","article-title":"Responses to Leishmania donovani in mice deficient in interleukin-12 (IL-12), IL-12\/IL-23, or IL-18","volume":"74","author":"HW Murray","year":"2006","journal-title":"Infect Immun"},{"key":"ref43","unstructured":"Saltelli A, Chan K, Scott EM (2000) Sensitivity Analysis: John Wiley &amp; Sons."},{"key":"ref44","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.immuni.2012.05.015","article-title":"CD4+ T cells rely on a cytokine gradient to control intracellular pathogens beyond sites of antigen presentation","volume":"37","author":"AJ Muller","year":"2012","journal-title":"Immunity"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1093\/infdis\/173.4.1041","article-title":"Models of relapse of experimental visceral leishmaniasis","volume":"173","author":"HW Murray","year":"1996","journal-title":"J Infect Dis"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/nri2448","article-title":"Exploring the full spectrum of macrophage activation","volume":"8","author":"DM Mosser","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1002\/1521-4141(2001010)31:10<2848::AID-IMMU2848>3.0.CO;2-T","article-title":"IL-10 mediates susceptibility to Leishmania donovani infection","volume":"31","author":"ML Murphy","year":"2001","journal-title":"Eur J Immunol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"6284","DOI":"10.1128\/IAI.70.11.6284-6293.2002","article-title":"Interleukin-10 (IL-10) in experimental visceral leishmaniasis and IL-10 receptor blockade as immunotherapy","volume":"70","author":"HW Murray","year":"2002","journal-title":"Infect Immun"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"5849","DOI":"10.4049\/jimmunol.0902024","article-title":"Murine Kupffer cells are protective in total hepatic ischemia\/reperfusion injury with bowel congestion through IL-10","volume":"184","author":"JD Ellett","year":"2010","journal-title":"J Immunol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.4049\/jimmunol.167.7.3919","article-title":"Critical role of Kupffer cell-derived IL-10 for host defense in septic peritonitis","volume":"167","author":"K Emmanuilidis","year":"2001","journal-title":"J Immunol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3389\/fimmu.2012.00172","article-title":"Pairing experimentation and computational modeling to understand the role of tissue inducer cells in the development of lymphoid organs","volume":"3","author":"K Alden","year":"2012","journal-title":"Front Immunol"},{"key":"ref52","article-title":"Extrinsic and intrinsic control of macrophage inflammatory responses","author":"HB Cohen","year":"2013","journal-title":"J Leukoc Biol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1161\/ATVBAHA.113.301453","article-title":"Transcriptional control of macrophage polarization","volume":"33","author":"D Tugal","year":"2013","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"11246","DOI":"10.1073\/pnas.0904846106","article-title":"Modeling the immune rheostat of macrophages in the lung in response to infection","volume":"106","author":"J Day","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"e68680","DOI":"10.1371\/journal.pone.0068680","article-title":"Multi-scale modeling predicts a balance of tumor necrosis factor-alpha and interleukin-10 controls the granuloma environment during Mycobacterium tuberculosis infection","volume":"8","author":"NA Cilfone","year":"2013","journal-title":"PLoS One"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1093\/bioinformatics\/btq050","article-title":"Snoopy\u2013a unifying Petri net framework to investigate biomolecular networks","volume":"26","author":"C Rohr","year":"2010","journal-title":"Bioinformatics"},{"key":"ref57","first-page":"222","article-title":"Pathologic changes in murine leishmaniasis (Leishmania donovani) with special reference to the dynamics of granuloma formation in the liver","volume":"114","author":"Y Gutierrez","year":"1984","journal-title":"Am J Pathol"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.4269\/ajtmh.2006.74.1013","article-title":"Responses to Leishmania donovani in mice deficient in both phagocyte oxidase and inducible nitric oxide synthase","volume":"74","author":"HW Murray","year":"2006","journal-title":"Am J Trop Med Hyg"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1084\/jem.20040704","article-title":"A subset of liver NK T cells is activated during Leishmania donovani infection by CD1d-bound lipophosphoglycan","volume":"200","author":"JL Amprey","year":"2004","journal-title":"J Exp Med"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/eji.200939863","article-title":"Leishmania donovani-induced expression of signal regulatory protein alpha on Kupffer cells enhances hepatic invariant NKT-cell activation","volume":"40","author":"L Beattie","year":"2010","journal-title":"Eur J Immunol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"e1000028","DOI":"10.1371\/journal.ppat.1000028","article-title":"Activation of invariant NKT cells exacerbates experimental visceral leishmaniasis","volume":"4","author":"AC Stanley","year":"2008","journal-title":"PLoS Pathog"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003334","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T08:53:47Z","timestamp":1688806427000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003334"}},"subtitle":[],"editor":[{"given":"Denis","family":"Thieffry","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2013,11,21]]},"references-count":61,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2013,11,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1003334","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,21]]}}}