{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T21:23:13Z","timestamp":1769721793090,"version":"3.49.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T00:00:00Z","timestamp":1399334400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0096527","type":"journal-article","created":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T20:42:58Z","timestamp":1399408978000},"page":"e96527","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Toxoplasma gondii 70 kDa Heat Shock Protein: Systemic Detection Is Associated with the Death of the Parasites by the Immune Response and Its Increased Expression in the Brain Is Associated with Parasite Replication"],"prefix":"10.1371","volume":"9","author":[{"given":"Paulo Victor Czarnewski","family":"Barenco","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine Vicente","family":"Louren\u00e7o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jair Pereira","family":"Cunha-J\u00fanior","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karine Cristine","family":"Almeida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cristina","family":"Roque-Barreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deise Aparecida Oliveira","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ester Cristina Borges","family":"Ara\u00fajo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loyane Bertagnolli","family":"Coutinho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rio C\u00e9zar","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiago Wilson Patriarca","family":"Mineo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Roberto","family":"Mineo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neide Maria","family":"Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2014,5,6]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.ijpara.2009.02.004","article-title":"Toxoplasmosis: A history of clinical observations","volume":"39","author":"LM Weiss","year":"2009","journal-title":"Int J Parasitol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1128\/IAI.66.7.3295-3302.1998","article-title":"Bradyzoite development in <italic>Toxoplasma gondii<\/italic> and the hsp70 stress response","volume":"66","author":"LM Weiss","year":"1998","journal-title":"Infect Immun"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"3959","DOI":"10.1128\/IAI.66.8.3959-3963.1998","article-title":"Expression of <italic>Toxoplasma gondii<\/italic>-specific heat shock protein 70 during In vivo conversion of bradyzoites to tachyzoites","volume":"66","author":"NM Silva","year":"1998","journal-title":"Infect Immun"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.exppara.2009.01.011","article-title":"<italic>Toxoplasma gondii<\/italic>: proteomic analysis of antigenicity of soluble tachyzoite antigen","volume":"122","author":"GY Ma","year":"2009","journal-title":"Exp Parasitol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"958","DOI":"10.4049\/jimmunol.169.2.958","article-title":"Heat shock protein 70 is a potential virulence factor in murine <italic>Toxoplasma<\/italic> infection via immunomodulation of host NF-kappa B and nitric oxide","volume":"169","author":"CA Dobbin","year":"2002","journal-title":"J Immunol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1379\/1466-1268(2000)005<0328:TGHAAD>2.0.CO;2","article-title":"<italic>Toxoplasma gondii<\/italic> Hsp70 as a danger signal in toxoplasma gondii-infected mice","volume":"5","author":"HS Mun","year":"2000","journal-title":"Cell Stress Chaperones"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"4634","DOI":"10.1128\/IAI.73.8.4634-4642.2005","article-title":"Toll-like receptor 4 mediates tolerance in macrophages stimulated with <italic>Toxoplasma gondii<\/italic>-derived heat shock protein 70","volume":"73","author":"HS Mun","year":"2005","journal-title":"Infect Immun"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1379\/1466-1268(2002)007<0357:TGDHSP>2.0.CO;2","article-title":"<italic>Toxoplasma gondii<\/italic>-derived heat shock protein HSP70 functions as a B cell mitogen","volume":"7","author":"F Aosai","year":"2002","journal-title":"Cell Stress Chaperones"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1379\/CSC-138R.1","article-title":"<italic>Toxoplasma gondii<\/italic>-derived heat shock protein 70 stimulates maturation of murine bone marrow-derived dendritic cells via Toll-like receptor 4","volume":"11","author":"F Aosai","year":"2006","journal-title":"Cell Stress Chaperones"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1093\/intimm\/dxg004","article-title":"The role of anti-HSP70 autoantibody-forming V(H)1-J(H)1 B-1 cells in <italic>Toxoplasma gondii<\/italic>-infected mice","volume":"15","author":"M Chen","year":"2003","journal-title":"Int Immunol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/j.1348-0421.1999.tb02430.x","article-title":"Role of Toxoplasma gondii HSP70 and Toxoplasma gondii HSP30\/bag1 in antibody formation and prophylactic immunity in mice experimentally infected with Toxoplasma gondii","volume":"43","author":"HS Mun","year":"1999","journal-title":"Microbiol Immunol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev-food-022811-101137","article-title":"Egg yolk antibodies for passive immunity","volume":"3","author":"J Kovacs-Nolan","year":"2012","journal-title":"Annu Rev Food Sci Technol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.biologicals.2012.05.003","article-title":"Avian IgY antibodies and their recombinant equivalents in research, diagnostics and therapy","volume":"40","author":"E Spillner","year":"2012","journal-title":"Biologicals"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e40391","DOI":"10.1371\/journal.pone.0040391","article-title":"Production, characterization and applications for <italic>Toxoplasma gondii<\/italic>-specific polyclonal chicken egg yolk immunoglobulins","volume":"7","author":"A Ferreira Junior","year":"2012","journal-title":"PLoS One"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.placenta.2006.10.011","article-title":"Susceptibility to vertical transmission of <italic>Toxoplasma gondii<\/italic> is temporally dependent on the preconceptional infection in <italic>Calomys callosus<\/italic>","volume":"28","author":"BF Barbosa","year":"2007","journal-title":"Placenta"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.vetpar.2006.08.028","article-title":"Evaluation of serological tests for the diagnosis of <italic>Neospora caninum<\/italic> infection in dogs: optimization of cut off titers and inhibition studies of cross-reactivity with <italic>Toxoplasma gondii<\/italic>","volume":"143","author":"DA Silva","year":"2007","journal-title":"Vet Parasitol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"286","DOI":"10.4049\/jimmunol.146.1.286","article-title":"Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated <italic>Toxoplasma gondii<\/italic> vaccine","volume":"146","author":"RT Gazzinelli","year":"1991","journal-title":"J Immunol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"MM Bradford","year":"1976","journal-title":"Anal Biochem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3347\/kjp.2006.44.3.209","article-title":"Cytokine and antibody responses of reactivated murine toxoplasmosis upon administration of dexamathasone","volume":"44","author":"KN Kang","year":"2006","journal-title":"Korean J Parasitol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1017\/S0031182006000539","article-title":"Long-term passage of tachyzoites in tissue culture can attenuate virulence of <italic>Neospora caninum<\/italic> in vivo","volume":"133","author":"PM Bartley","year":"2006","journal-title":"Parasitology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.exppara.2009.05.011","article-title":"<italic>Toxoplasma gondii<\/italic>: the role of IFN-gamma, TNFRp55 and iNOS in inflammatory changes during infection","volume":"123","author":"NM Silva","year":"2009","journal-title":"Exp Parasitol"},{"key":"ref22","first-page":"291","article-title":"Quantification of histochemical staining by color deconvolution","volume":"23","author":"AC Ruifrok","year":"2001","journal-title":"Anal Quant Cytol Histol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.ijpara.2012.01.006","article-title":"The impaired pregnancy outcome in murine congenital toxoplasmosis is associated with a pro-inflammatory immune response, but not correlated with decidual inducible nitric oxide synthase expression","volume":"42","author":"LB Coutinho","year":"2012","journal-title":"Int J Parasitol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1590\/S0036-46651999000600001","article-title":"Detection of <italic>Toxoplasma gondii<\/italic> soluble antigen, SAG-1(p30), antibody and immune complex in the cerebrospinal fluid of HIV positive or negative individuals","volume":"41","author":"FA Chaves-Borges","year":"1999","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3382\/ps.2008-00323","article-title":"Monitoring of laying capacity, immunoglobulin Y concentration, and antibody titer development in chickens immunized with ricin and botulinum toxins over a two-year period","volume":"88","author":"D Pauly","year":"2009","journal-title":"Poult Sci"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1099\/jmm.0.04978-0","article-title":"Identification of immunodominant <italic>Helicobacter pylori<\/italic> proteins with reactivity to <italic>H. pylori<\/italic>-specific egg-yolk immunoglobulin","volume":"52","author":"JH Shin","year":"2003","journal-title":"J Med Microbiol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0022-1759(93)90179-B","article-title":"Comparison of four purification methods for the production of immunoglobulins from eggs laid by hens immunized with an enterotoxigenic <italic>E. coli<\/italic> strain","volume":"160","author":"EM Akita","year":"1993","journal-title":"J Immunol Methods"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1099\/00222615-46-3-263","article-title":"A mouse model of recrudescence of <italic>Toxoplasma gondii<\/italic> infection","volume":"46","author":"S Nicoll","year":"1997","journal-title":"J Med Microbiol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.exppara.2010.04.003","article-title":"Recrudescence of <italic>Toxoplasma gondii<\/italic> infection in chronically infected rats (Rattus norvegicus)","volume":"125","author":"RC Silva","year":"2010","journal-title":"Exp Parasitol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.exppara.2009.10.003","article-title":"<italic>Toxoplasma gondii<\/italic>: Simple duplex RT-PCR assay for detecting SAG1 and BAG1 genes during stage conversion in immunosuppressed mice","volume":"124","author":"A Mahittikorn","year":"2010","journal-title":"Exp Parasitol"},{"key":"ref32","first-page":"99","article-title":"Murine Model of Drug-induced Reactivation of <italic>Toxoplasma gondii<\/italic>","volume":"40","author":"O Djurkovic-Djakovic","year":"2001","journal-title":"Acta Protozoologica"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.exppara.2010.04.019","article-title":"<italic>Toxoplasma gondii<\/italic>: the severity of toxoplasmic encephalitis in C57BL\/6 mice is associated with increased ALCAM and VCAM-1 expression in the central nervous system and higher blood-brain barrier permeability","volume":"126","author":"NM Silva","year":"2010","journal-title":"Exp Parasitol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1128\/CVI.00117-13","article-title":"<italic>Toxoplasma gondii<\/italic> recombinant antigens as tools for serodiagnosis of human toxoplasmosis - the current status of studies","volume":"20","author":"L Holec-Gasior","year":"2013","journal-title":"Clin Vaccine Immunol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.exppara.2006.03.011","article-title":"<italic>Toxoplasma gondii<\/italic>: an evaluation of diagnostic value of recombinant antigens in a murine model","volume":"114","author":"J Gatkowska","year":"2006","journal-title":"Exp Parasitol"},{"key":"ref36","unstructured":"Reichard U, Gross U (2007) <italic>Toxoplasma<\/italic> animal models and therapeutics. In: Weiss LM, Kim K, editors. <italic>Toxoplasma gondii<\/italic>: the model Apicomplexan: perspectives and methods. London: Elsevier. pp. 153\u2013177."},{"key":"ref37","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/334255a0","article-title":"Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells","volume":"334","author":"TL Stevens","year":"1988","journal-title":"Nature"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s12010-012-9648-1","article-title":"Development of DNA-designed avian IgY antibodies for detection of <italic>Mycobacterium avium<\/italic> subsp. paratuberculosis heat shock protein 70 (Hsp70) and anti-Hsp70 antibodies in the serum of normal cattle","volume":"167","author":"GN Brujeni","year":"2012","journal-title":"Appl Biochem Biotechnol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.parint.2012.01.008","article-title":"Chicken egg yolk antibodies (IgY) for detecting circulating antigens of <italic>Schistosoma japonicum<\/italic>","volume":"61","author":"YC Cai","year":"2012","journal-title":"Parasitol Int"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1365-3024.1995.tb00902.x","article-title":"Heat shock proteins of <italic>Toxoplasma gondii<\/italic>","volume":"17","author":"RE Lyons","year":"1995","journal-title":"Parasite Immunol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/S0020-7519(98)00074-5","article-title":"Gene sequence and transcription differences in 70 kDa heat shock protein correlate with murine virulence of <italic>Toxoplasma gondii<\/italic>","volume":"28","author":"RE Lyons","year":"1998","journal-title":"Int J Parasitol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.exppara.2012.05.006","article-title":"Kinetics of parasite burdens in blood and tissues during murine toxoplasmosis","volume":"131","author":"O Djurkovic-Djakovic","year":"2012","journal-title":"Exp Parasitol"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Cruse JC, Lewis RE (2010) Antigen-antibody interactions. In: Cruse JC, Lewis RE, editors. Atlas of Immunology. Boca Raton: CRC Press. pp. 285\u2013306.","DOI":"10.1201\/EBK1439802687-c8"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1128\/JCM.22.4.645-650.1985","article-title":"Demonstration of Toxoplasma antigen containing complexes in active toxoplasmosis","volume":"22","author":"F van Knapen","year":"1985","journal-title":"J Clin Microbiol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2460\/ajvr.1993.54.03.415","article-title":"Detection of <italic>Toxoplasma gondii<\/italic> antigen-containing immune complexes in the serum of cats","volume":"54","author":"MR Lappin","year":"1993","journal-title":"Am J Vet Res"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.4049\/jimmunol.151.7.3672","article-title":"Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-alpha and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation","volume":"151","author":"RT Gazzinelli","year":"1993","journal-title":"J Immunol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"175","DOI":"10.4049\/jimmunol.149.1.175","article-title":"Simultaneous depletion of CD4+ and CD8+ T lymphocytes is required to reactivate chronic infection with Toxoplasma gondii","volume":"149","author":"R Gazzinelli","year":"1992","journal-title":"J Immunol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.ijpara.2007.09.017","article-title":"Detection of the initial site of <italic>Toxoplasma gondii<\/italic> reactivation in brain tissue","volume":"38","author":"Y Takashima","year":"2008","journal-title":"Int J Parasitol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/nri1810","article-title":"Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens","volume":"6","author":"EM Sternberg","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/ncpneuro0810","article-title":"Steroids and immunosuppressant drugs in myasthenia gravis","volume":"4","author":"S Sathasivam","year":"2008","journal-title":"Nat Clin Pract Neurol"},{"key":"ref51","first-page":"725","article-title":"Immunosuppression in liver transplantation","volume":"58","author":"GT Everson","year":"2003","journal-title":"Minerva Chir"},{"key":"ref52","first-page":"1135","article-title":"Randomized, double-blind, split-side, comparison study of moisturizer containing licochalcone A and 1% hydrocortisone in the treatment of childhood atopic dermatitis","volume":"96","author":"S Wananukul","year":"2013","journal-title":"J Med Assoc Thai"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1034\/j.1399-3062.2001.003001024.x","article-title":"Disseminated toxoplasmosis after bone marrow transplantation: report of 9 cases","volume":"3","author":"BC de Medeiros","year":"2001","journal-title":"Transpl Infect Dis"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.pharmthera.2012.08.014","article-title":"Comprehensive review on the HSC70 functions, interactions with related molecules and involvement in clinical diseases and therapeutic potential","volume":"136","author":"T Liu","year":"2012","journal-title":"Pharmacol Ther"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1574-695X.2009.00639.x","article-title":"Plasmodial heat shock proteins: targets for chemotherapy","volume":"58","author":"A Shonhai","year":"2010","journal-title":"FEMS Immunol Med Microbiol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0096527","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,26]],"date-time":"2024-05-26T13:13:36Z","timestamp":1716729216000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0096527"}},"subtitle":[],"editor":[{"given":"Stanislas","family":"Tomavo","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2014,5,6]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2014,5,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0096527","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,6]]}}}