{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:21Z","timestamp":1787026581409,"version":"build-2736575974"},"reference-count":120,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Chagas\u2019 disease is a zoonotic parasitic ailment now affecting more than 6 million people, mainly in Latin America. Its agent, the protozoan\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    , is primarily transmitted by endemic hematophagous triatomine insects. Transplacental transmission is also important and a main source for the emerging global expansion of this disease. In the host, the parasite undergoes intra (amastigotes) and extracellular infective (trypomastigotes) stages, both eliciting complex immune responses that, in about 70% of the cases, culminate in permanent immunity, concomitant with the asymptomatic presence of the parasite. The remaining 30% of those infected individuals will develop a syndrome, with variable pathological effects on the circulatory, nervous, and digestive systems. Herein, we review an important number of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    molecules, mainly located on its surface, that have been characterized as immunogenic and protective in various experimental setups. We also discuss a variety of parasite strategies to evade the complement system - mediated immune responses. Within this context, we also discuss the capacity of the\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infective trypomastigote to translocate the ER-resident chaperone calreticulin to its surface as a key evasive strategy. Herein, it is described that\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    calreticulin inhibits the initial stages of activation of the host complement system, with obvious benefits for the parasite. Finally, we speculate on the possibility to experimentally intervene in the interaction of calreticulin and other\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    molecules that interact with the complement system; thus resulting in significant inhibition of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infectivity.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.789145","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T05:29:54Z","timestamp":1639632594000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Is It Possible to Intervene in the Capacity of Trypanosoma cruzi to Elicit and Evade the Complement System?"],"prefix":"10.3389","volume":"12","author":[{"given":"Galia","family":"Ram\u00edrez-Toloza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Aguilar-Guzm\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Valck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smrithi S.","family":"Menon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana P.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.16-0225","article-title":"Meningoencephalitis Caused by Reactivation of Chagas Disease in Patient Without Known Immunosuppression","volume":"96","author":"Fernandes","year":"2017","journal-title":"Am J Trop Med Hyg"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2450\/2015.0040-15","article-title":"Chagas Disease and Transfusion Medicine: A Perspective From Non-Endemic Countries","volume":"13","author":"Angheben","year":"2015","journal-title":"Blood Transfus"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0009697","article-title":"The Chagas Disease Study Landscape: A Systematic Review of Clinical and Observational Antiparasitic Treatment Studies to Assess the Potential for Establishing an Individual Participant-Level Data Platform","volume":"15","author":"Maguire","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"key":"B4","unstructured":"Chagas Disease (Also Known as American Trypanosomiasis)2021"},{"key":"B5","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13071-020-04534-z","article-title":"Trypanosoma cruzi Infection in Triatoma Infestans and High Levels of Human\u2013Vector Contact Across a Rural-to-Urban Gradient in the Argentine Chaco","volume":"14","author":"Alvedro","year":"2021","journal-title":"Parasit Vectors"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1017\/s0031182013002199","article-title":"Modelling Inter-Human Transmission Dynamics of Chagas Disease: Analysis and Application","volume":"141","author":"Fabrizio","year":"2014","journal-title":"Parasitology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s40615-017-0362-0","article-title":"Chagas Disease Knowledge and Risk Behaviors of the Homeless Population in Houston, TX","volume":"5","author":"Ingber","year":"2018","journal-title":"J Racial Ethn Health Dispar"},{"key":"B8","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.pt.2015.06.006","article-title":"Reactivation of Chagas Disease: Implications for Global Health","volume":"31","author":"Perez","year":"2015","journal-title":"Trends Parasitol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1993.49.370","article-title":"Humoral and Cellular Immune Response of Adults From Northeastern Brazil With Chronic Trypanosoma cruzi Infection: Depressed Cellular Immune Response to T. cruzi Antigen Among Chagas\u2019 Disease Patients With Symptomatic Versus Indeterminate Infection","volume":"49","author":"Cetron","year":"1993","journal-title":"Am J Trop Med Hyg"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/iai.31.3.1117-1124.1981","article-title":"Experimental Chagas\u2019 Disease: Kinetics of Lymphocyte Responses and Immunological Control of the Transition From Acute to Chronic Trypanosoma cruzi Infection","volume":"31","author":"Hayes","year":"1981","journal-title":"Infect Immun"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01150.x","article-title":"Trypanosoma cruzi-Induced Immunosuppression: B Cells Undergo Spontaneous Apoptosis and Lipopolysaccharide (LPS) Arrests Their Proliferation During Acute Infection","volume":"119","author":"Zu\u00f1iga","year":"2000","journal-title":"Clin Exp Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/14779072.2017.1317591","article-title":"Chagas Disease Immunogenetics: Elusive Markers of Disease Progression","volume":"15","author":"Ortega Zamora","year":"2017","journal-title":"Expert Rev Cardiovasc Ther"},{"key":"B13","article-title":"Study on the Liturgical Action of Different Places on the Culture and Blood Forms of Schizotrypanum cruzi","volume":"5","author":"Muniz","year":"1945","journal-title":"Rev Bras Biol"},{"key":"B14","article-title":"Lytic Effect of Normal Sera on Cultured and Sanguineous Forms of Trypanosoma cruzi","volume":"11","author":"Rubio","year":"1956","journal-title":"Bol Chil Parasitol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009721","article-title":"Inefficient Complement System Clearance of Trypanosoma cruzi Metacyclic Trypomastigotes Enables Resistant Strains to Invade Eukaryotic Cells","volume":"5","author":"Cestari","year":"2010","journal-title":"PLoS One"},{"key":"B16","first-page":"299","article-title":"Gp 58\/68, a Parasite Component That Contributes to the Escape of the Trypomastigote Form of T. cruzi From Damage by the Human Alternative Complement Pathway","volume":"65","author":"Fischer","year":"1988","journal-title":"Immunology"},{"key":"B17","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.147.7.2240","article-title":"Characterization of a Trypanosoma cruzi C3 Binding Protein With Functional and Genetic Similarities to the Human Complement Regulatory Protein, Decay-Accelerating Factor","volume":"147","author":"Norris","year":"1991","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.1.236-243.1994","article-title":"Biochemical Analysis of the Membrane and Soluble Forms of the Complement Regulatory Protein of Trypanosoma cruzi","volume":"62","author":"Norris","year":"1994","journal-title":"Infect Immun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/s1046-5928(02)00562-4","article-title":"Expression and Purification of Functional, Recombinant Trypanosoma cruzi Complement Regulatory Protein","volume":"27","author":"Beucher","year":"2003","journal-title":"Protein Expr Purif"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02761988000500069","article-title":"Identification of Membrane Components of Trypanosoma cruzi Modulators of Complement System","volume":"83","author":"Kipnis","year":"1988","journal-title":"Memorias do Inst Oswaldo Cruz"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.9.3656-3663.1993","article-title":"A Partial cDNA Clone of Trypomastigote Decay-Accelerating Factor (T-DAF), a Developmentally Regulated Complement Inhibitor of Trypanosoma cruzi, has Genetic and Functional Similarities to the Human Complement Inhibitor DAF","volume":"61","author":"Tambourgi","year":"1993","journal-title":"Infect Immun"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.3042","article-title":"The Classical Activation Pathway of the Human Complement System Is Specifically Inhibited by Calreticulin From Trypanosoma cruzi","volume":"172","author":"Ferreira","year":"2004","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1086\/592167","article-title":"Complement C2 Receptor Inhibitor Trispanning Confers an Increased Ability to Resist Complement-Mediated Lysis in Trypanosoma cruzi","volume":"198","author":"Cestari Idos","year":"2008","journal-title":"J Infect Dis"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2009.08.030","article-title":"Role of Early Lectin Pathway Activation in the Complement-Mediated Killing of Trypanosoma cruzi","volume":"47","author":"Cestari Idos","year":"2009","journal-title":"Mol Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e730","DOI":"10.1371\/journal.pntd.0000730","article-title":"Antiangiogenic and Antitumor Effects of Trypanosoma cruzi Calreticulin","volume":"4","author":"Lopez","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002696","article-title":"A Monoallelic Deletion of the TcCRT Gene Increases the Attenuation of a Cultured Trypanosoma cruzi Strain, Protecting Against an In Vivo Virulent Challenge","volume":"8","author":"Sanchez-Valdez","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2010.01.019","article-title":"Molecular Mechanisms Involved in the Inactivation of the First Component of Human Complement by Trypanosoma cruzi Calreticulin","volume":"47","author":"Valck","year":"2010","journal-title":"Mol Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2014.03.014","article-title":"Trypanosoma cruzi Calreticulin Inhibits the Complement Lectin Pathway Activation by Direct Interaction With L-Ficolin","volume":"60","author":"Sosoniuk","year":"2014","journal-title":"Mol Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2010.04.001","article-title":"Trypanosoma cruzi Calreticulin: A Novel Virulence Factor That Binds Complement C1 on the Parasite Surface and Promotes Infectivity","volume":"216","author":"Ramirez","year":"2011","journal-title":"Immunobiology"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1995.52.516","article-title":"Detection of Trypanosoma-Decay Accelerating Factor Antibodies in Mice and Humans Infected With Trypanosoma cruzi","volume":"52","author":"Tambourgi","year":"1995","journal-title":"Am J Trop Med Hyg"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.6.2460-2465.1998","article-title":"Stable Transfection of Trypanosoma cruzi Epimastigotes With the Trypomastigote-Specific Complement Regulatory Protein cDNA Confers Complement Resistance","volume":"66","author":"Norris","year":"1998","journal-title":"Infect Immun"},{"key":"B32","article-title":"Human and Mouse Sera Recognize the Same Polypeptide Associated With Immunological Resistance to Trypanosoma cruzi Infection","volume":"61","author":"Martins","year":"1985","journal-title":"Clin Exp Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1128\/iai.68.9.4986-4991.2000","article-title":"DNA-Based Immunization With Trypanosoma cruzi Complement Regulatory Protein Elicits Complement Lytic Antibodies and Confers Protection Against Trypanosoma cruzi Infection","volume":"68","author":"Sepulveda","year":"2000","journal-title":"Infect Immun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2017.12.003","article-title":"Use of Tc-rCRP as a Target for Lytic Antibody Titration After Experimental Trypanosoma cruzi Infection","volume":"184","author":"Marques","year":"2018","journal-title":"Exp Parasitol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1017\/s0031182000058467","article-title":"Identification and Isolation of Trypanosoma cruzi Trypomastigote Collagen-Binding Proteins: Possible Role in Cell-Parasite Interaction","volume":"97","author":"Velge","year":"1988","journal-title":"Parasitology"},{"key":"B36","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.137.5.1623","article-title":"Mechanism of Resistance to Lysis by the Alternative Complement Pathway in Trypanosoma cruzi Trypomastigotes: Effect of Specific Monoclonal Antibody","volume":"137","author":"Schenkman","year":"1986","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102053","article-title":"Trypanosoma cruzi Immune Evasion Mediated by Host Cell-Derived Microvesicles","volume":"188","author":"Cestari","year":"2012","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.10.5213","article-title":"Complement C2 Receptor Inhibitor Trispanning and the Beta-Chain of C4 Share a Binding Site for Complement C2","volume":"168","author":"Inal","year":"2002","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01304-1","article-title":"Sim RB. A Schistosoma Protein, Sh-TOR, Is a Novel Inhibitor of Complement Which Binds Human C2","volume":"470","author":"Inal","year":"2000","journal-title":"FEBS Lett"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-005-0009-9","article-title":"Complement C2 Receptor Inhibitor Trispanning: From Man to Schistosome","volume":"27","author":"Inal","year":"2005","journal-title":"Springer Semin Immunopathol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760170332","article-title":"Complement System Contributes to Modulate the Infectivity of Susceptible TcI Strains of Trypanosoma cruzi","volume":"113","author":"Arroyo-Olarte","year":"2018","journal-title":"Memorias do Inst Oswaldo Cruz"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2004.12.014","article-title":"An In Vivo Role for Trypanosoma cruzi Calreticulin in Antiangiogenesis","volume":"140","author":"Molina","year":"2005","journal-title":"Mol Biochem Parasitol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.4067\/S0716-97602010000300004","article-title":"Comparative In Vivo Antiangiogenic Effects of Calreticulin From Trypanosoma cruzi and Homo Sapiens Sapiens","volume":"43","author":"Toledo","year":"2010","journal-title":"Biol Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1186\/s12885-016-2764-5","article-title":"Does Native Trypanosoma cruzi Calreticulin Mediate Growth Inhibition of a Mammary Tumor During Infection","volume":"16","author":"Abello-Caceres","year":"2016","journal-title":"BMC Cancer"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1023\/A:1016636419597","article-title":"Anticancer Properties of Flagellate Protozoan Trypanosoma cruzi chagas, 1909","volume":"28","author":"Kallinikova","year":"2001","journal-title":"Biol Bull Russian Acad Sci"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1126\/science.107.2788.600","article-title":"Trypanosoma cruzi Endotoxin (KR) in the Treatment of Malignant Mouse Tumors","volume":"107","author":"Hauschka","year":"1948","journal-title":"Science"},{"key":"B47","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.molimm.2012.08.001","article-title":"Trypanosoma cruzi Carrying a Monoallelic Deletion of the Calreticulin (TcCRT) Gene Are Susceptible to Complement Mediated Killing and Defective in Their Metacyclogenesis","volume":"53","author":"Sanchez Valdez","year":"2013","journal-title":"Mol Immunol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"295","DOI":"10.4269\/ajtmh.16-0642","article-title":"Triatoma Infestans Calreticulin: Gene Cloning and Expression of a Main Domain That Interacts With the Host Complement System","volume":"96","author":"Weinberger","year":"2016","journal-title":"Am J Trop Med Hyg"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-004-0724-7","article-title":"Immunocytochemical Localisation of Calreticulin in Trypanosoma cruzi","volume":"122","author":"Souto-Padron","year":"2004","journal-title":"Histochem Cell Biol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.14-0497","article-title":"Trypanosoma cruzi Calreticulin Topographical Variations in Parasites Infecting Murine Macrophages","volume":"92","author":"Gonzalez","year":"2015","journal-title":"Am J Trop Med Hyg"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.08.032","article-title":"Cell-Surface Calreticulin Initiates Clearance of Viable or Apoptotic Cells Through Trans-Activation of LRP on the Phagocyte","volume":"123","author":"Gardai","year":"2005","journal-title":"Cell"},{"key":"B52","article-title":"Collectin Receptor (C1q Receptor): Structure and Function","author":"Malhotra","year":"1993","journal-title":"Behring Inst Mitt"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.4067\/s0716-97602005000200008","article-title":"F(ab\u2019)2 Antibody Fragments Against Trypanosoma cruzi Calreticulin Inhibit Its Interaction With the First Component of Human Complement","volume":"38","author":"Aguilar","year":"2005","journal-title":"Biol Res"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2016.10.020","article-title":"Exogenous Calreticulin, Incorporated Onto Non-Infective Trypanosoma cruzi Epimastigotes, Promotes Their Internalization Into Mammal Host Cells","volume":"222","author":"Sosoniuk-Roche","year":"2017","journal-title":"Immunobiology"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2012.02.003","article-title":"Calreticulin has Opposing Effects on the Migration of Human Trophoblast and Myometrial Endothelial Cells","volume":"33","author":"Crawford","year":"2012","journal-title":"Placenta"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gan017","article-title":"Calreticulin in Human Pregnancy and Pre-Eclampsia","volume":"14","author":"Gu","year":"2008","journal-title":"Mol Hum Reprod"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3891\/acta.chem.scand.48-0905","article-title":"Human Placental Calreticulin: Purification, Characterization and Association With Other Proteins","volume":"48","author":"Houen","year":"1994","journal-title":"Acta Chem Scand"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002376","article-title":"The Interaction of Classical Complement Component C1 With Parasite and Host Calreticulin Mediates Trypanosoma cruzi Infection of Human Placenta","volume":"7","author":"Castillo","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0009281","article-title":"Chagas Disease Screening in Pregnant Latin American Women: Adherence to a Systematic Screening Protocol in a Non-Endemic Country","volume":"15","author":"Llenas-Garc\u00eda","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2014.01.054","article-title":"Differential Ability to Resist to Complement Lysis and Invade Host Cells Mediated by MBL in R4 and 860 Strains of Trypanosoma cruzi","volume":"588","author":"Evans-Osses","year":"2014","journal-title":"FEBS Lett"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.14-0236","article-title":"Deficiency in Mannose-Binding Lectin-Associated Serine Protease-2 Does Not Increase Susceptibility to Trypanosoma cruzi Infection","volume":"92","author":"Ribeiro","year":"2015","journal-title":"Am J Trop Med Hyg"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060237","article-title":"Association of L-Ficolin Levels and FCN2 Genotypes With Chronic Chagas Disease","volume":"8","author":"Luz","year":"2013","journal-title":"PLoS One"},{"key":"B63","doi-asserted-by":"publisher","first-page":"151863","DOI":"10.1016\/j.imbio.2019.10.012","article-title":"Structural Bases That Underline Trypanosoma cruzi Calreticulin Proinfective, Antiangiogenic and Antitumor Properties","volume":"225","author":"Pe\u00f1a \u00c1lvarez","year":"2020","journal-title":"Immunobiology"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1107\/s2052252516012847","article-title":"Structures of Parasite Calreticulins Provide Insights Into Their Flexibility and Dual Carbohydrate\/Peptide-Binding Properties","volume":"3","author":"Moreau","year":"2016","journal-title":"IUCrJ"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1084\/jem.166.5.1221","article-title":"The Mechanism of Action of Decay-Accelerating Factor (DAF). DAF Inhibits the Assembly of C3 Convertases by Dissociating C2a and Bb","volume":"166","author":"Fujita","year":"1987","journal-title":"J Exp Med"},{"key":"B66","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/0014-4894(89)90097-0","article-title":"Trypanosoma cruzi: Antibody-Dependent Killing of Bloodstream Trypomastigotes by Mouse Bone Marrow-Derived Mast Cells and by Mastocytoma Cells","volume":"68","author":"Tambourgi","year":"1989","journal-title":"Exp Parasitol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)37962-6","article-title":"Biochemical Characterization of a Factor Produced by Trypomastigotes of Trypanosoma cruzi That Accelerates the Decay of Complement C3 Convertases","volume":"263","author":"Joiner","year":"1988","journal-title":"J Biol Chem"},{"key":"B68","doi-asserted-by":"publisher","first-page":"e25914","DOI":"10.1371\/journal.pone.0025914","article-title":"Genomic Analyses, Gene Expression and Antigenic Profile of the Trans-Sialidase Superfamily of Trypanosoma cruzi Reveal an Undetected Level of Complexity","volume":"6","author":"Freitas","year":"2011","journal-title":"PLoS One"},{"key":"B69","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/0166-6851(85)90051-9","article-title":"Incorporation of Sialic Acid Into Trypanosoma cruzi Macromolecules. A Proposal for a New Metabolic Route","volume":"16","author":"Previato","year":"1985","journal-title":"Mol Biochem Parasitol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwv057","article-title":"The Trans-Sialidase, the Major Trypanosoma cruzi Virulence Factor: Three Decades of Studies","volume":"25","author":"Freire-de-Lima","year":"2015","journal-title":"Glycobiology"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1128\/iai.01104-07","article-title":"Sequence Diversity of the Trypanosoma cruzi Complement Regulatory Protein Family","volume":"76","author":"Beucher","year":"2008","journal-title":"Infect Immun"},{"key":"B72","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.exppara.2016.09.001","article-title":"Correlation Between the Virulence of T. cruzi Strains, Complement Regulatory Protein Expression Levels, and the Ability to Elicit Lytic Antibody Production","volume":"170","author":"Henrique","year":"2016","journal-title":"Exp Parasitol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2007.12.010","article-title":"Exploring the FL-160-CRP Gene Family Through Sequence Variability of the Complement Regulatory Protein (CRP) Expressed by the Trypomastigote Stage of Trypanosoma cruzi","volume":"8","author":"Mathieu-Daud\u00e9","year":"2008","journal-title":"Infect Genet Evol"},{"key":"B74","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.158.7.3293","article-title":"Delivery by Trypanosoma cruzi of Proteins Into the MHC Class I Antigen Processing and Presentation Pathway","volume":"158","author":"Garg","year":"1997","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2005.01.001","article-title":"Identification of Multiple HLA-A*0201-Restricted cruzipain and FL-160 CD8+ Epitopes Recognized by T Cells From Chronically Trypanosoma cruzi-Infected Patients","volume":"7","author":"Fonseca","year":"2005","journal-title":"Microbes Infect"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.11.3963","article-title":"Murine Protein H Is Comprised of 20 Repeating Units, 61 Amino Acids in Length","volume":"83","author":"Kristensen","year":"1986","journal-title":"Proc Natl Acad Sci USA"},{"key":"B77","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1042\/bj2490593","article-title":"The Complete Amino Acid Sequence of Human Complement Factor H","volume":"249","author":"Ripoche","year":"1988","journal-title":"Biochem J"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/s0162-3109(00)80300-8","article-title":"Host Recognition and Target Differentiation by Factor H, a Regulator of the Alternative Pathway of Complement","volume":"49","author":"Pangburn","year":"2000","journal-title":"Immunopharmacology"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.20.10996","article-title":"Identification of Three Physically and Functionally Distinct Binding Sites for C3b in Human Complement Factor H by Deletion Mutagenesis","volume":"93","author":"Sharma","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01728","article-title":"Characterization of Binding Properties of Individual Functional Sites of Human Complement Factor H","volume":"11","author":"Haque","year":"2020","journal-title":"Front Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1042\/bj2320841","article-title":"Structural and Functional Analysis of the Complement Component Factor H With the Use of Different Enzymes and Monoclonal Antibodies to Factor H","volume":"232","author":"Alsenz","year":"1985","journal-title":"Biochem J"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002903200","article-title":"Each of the Three Binding Sites on Complement Factor H Interacts With a Distinct Site on C3b","volume":"275","author":"Jokiranta","year":"2000","journal-title":"J Biol Chem"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)37905-5","article-title":"A Discontinuous Factor H Binding Site in the Third Component of Complement as Delineated by Synthetic Peptides","volume":"263","author":"Lambris","year":"1988","journal-title":"J Biol Chem"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1042\/bj2240389","article-title":"Localization of the Complement-Component-C3b-Binding Site and the Cofactor Activity for Factor I in the 38kda Tryptic Fragment of Factor H","volume":"224","author":"Alsenz","year":"1984","journal-title":"Biochem J"},{"key":"B85","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.155.12.5663","article-title":"Mapping of the Complement Regulatory Domains in the Human Factor H-Like Protein 1 and in Factor H1","volume":"155","author":"Kuhn","year":"1995","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90008-m","article-title":"A Novel Cell Surface Trans-Sialidase of Trypanosoma cruzi Generates a Stage-Specific Epitope Required for Invasion of Mammalian Cells","volume":"65","author":"Schenkman","year":"1991","journal-title":"Cell"},{"key":"B87","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.153.7.3141","article-title":"Role of Sialic Acid in the Resistance of Trypanosoma cruzi Trypomastigotes to Complement","volume":"153","author":"Tomlinson","year":"1994","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B88","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.128.3.1278","article-title":"Capsular Sialic Acid Prevents Activation of the Alternative Complement Pathway by Type III, Group B Streptococci","volume":"128","author":"Edwards","year":"1982","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.7.2866-2871.1993","article-title":"Capsular Polysaccharide Regulates Neutrophil Complement Receptor Interactions With Type III Group B Streptococci","volume":"61","author":"Edwards","year":"1993","journal-title":"Infect Immun"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.10.3986-3993.1992","article-title":"Prevention of C3 Deposition by Capsular Polysaccharide Is a Virulence Mechanism of Type III Group B Streptococci","volume":"60","author":"Marques","year":"1992","journal-title":"Infect Immun"},{"key":"B91","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1128\/iai.60.1.39-43.1992","article-title":"Gonococcal Lipooligosaccharide Sialylation Prevents Complement-Dependent Killing by Immune Sera","volume":"60","author":"Wetzler","year":"1992","journal-title":"Infect Immun"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.11.023","article-title":"Discrimination Between Host and Pathogens by the Complement System","volume":"26","author":"Pangburn","year":"2008","journal-title":"Vaccine"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1038\/nri2620","article-title":"Complement Regulators and Inhibitory Proteins","volume":"9","author":"Zipfel","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.1.602","article-title":"Enzymatic Treatment Transforms Trypomastigotes of Trypanosoma cruzi Into Activators of Alternative Complement Pathway and Potentiates Their Uptake by Macrophages","volume":"78","author":"Kipnis","year":"1981","journal-title":"Proc Natl Acad Sci USA"},{"key":"B95","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.137.9.2961","article-title":"Evasion of the Alternative Complement Pathway by Metacyclic Trypomastigotes of Trypanosoma cruzi: Dependence on the Developmentally Regulated Synthesis of Surface Protein and N-Linked Carbohydrate","volume":"137","author":"Sher","year":"1986","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03105","article-title":"Toxoplasma gondii Recruits Factor H and C4b-Binding Protein to Mediate Resistance to Serum Killing and Promote Parasite Persistence In Vivo","volume":"10","author":"Sikorski","year":"2019","journal-title":"Front Immunol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12535","article-title":"The Plasmodium falciparum Blood Stages Acquire Factor H Family Proteins to Evade Destruction by Human Complement","volume":"18","author":"Rosa","year":"2016","journal-title":"Cell Microbiol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy166","article-title":"Complement Factor H Levels Associate With Plasmodium falciparum Malaria Susceptibility and Severity","volume":"5","author":"van Beek","year":"2018","journal-title":"Open Forum Infect Dis"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501581","article-title":"Recruitment of Factor H as a Novel Complement Evasion Strategy for Blood-Stage Plasmodium falciparum Infection","volume":"196","author":"Kennedy","year":"2016","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B100","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.158.8.3779","article-title":"Complement Evasion by Echinococcus granulosus: Sequestration of Host Factor H in the Hydatid Cyst Wall","volume":"158","author":"D\u00edaz","year":"1997","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12537","article-title":"Complement Factor H as a Potential Atherogenic Marker in Chronic Chagas\u2019 Disease","volume":"40","author":"Lidani","year":"2018","journal-title":"Parasite Immunol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1725","article-title":"Intercellular Transfer of the Oncogenic Receptor EGFRvIII by Microvesicles Derived From Tumour Cells","volume":"10","author":"Al-Nedawi","year":"2008","journal-title":"Nat Cell Biol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.76","article-title":"Membrane Microparticles Mediate Transfer of P-Glycoprotein to Drug Sensitive Cancer Cells","volume":"23","author":"Bebawy","year":"2009","journal-title":"Leukemia"},{"key":"B104","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/s0002-9440(10)62253-5","article-title":"ABCA1 Gene Deletion Protects Against Cerebral Malaria: Potential Pathogenic Role of Microparticles in Neuropathology","volume":"166","author":"Combes","year":"2005","journal-title":"Am J Pathol"},{"key":"B105","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1172\/jci4985","article-title":"In Vitro Generation of Endothelial Microparticles and Possible Prothrombotic Activity in Patients With Lupus Anticoagulant","volume":"104","author":"Combes","year":"1999","journal-title":"J Clin Invest"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-135822","article-title":"Platelet Microparticles: A New Player in Malaria Parasite Cytoadherence to Human Brain Endothelium","volume":"23","author":"Faille","year":"2009","journal-title":"FASEB J"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001656","article-title":"Human Plasma Membrane-Derived Vesicles Halt Proliferation and Induce Differentiation of THP-1 Acute Monocytic Leukemia Cells","volume":"185","author":"Ansa-Addo","year":"2010","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4827(03)00055-7","article-title":"Characterisation and Properties of Ectosomes Released by Human Polymorphonuclear Neutrophils","volume":"285","author":"Gasser","year":"2003","journal-title":"Exp Cell Res"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-005-0004-1","article-title":"Emission of Membrane Vesicles: Roles in Complement Resistance, Immunity and Cancer","volume":"27","author":"Pilzer","year":"2005","journal-title":"Springer Semin Immunopathol"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2006.04.006","article-title":"Cell Vesiculation and Immunopathology: Implications in Cerebral Malaria","volume":"8","author":"Coltel","year":"2006","journal-title":"Microbes Infect"},{"key":"B111","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/978-1-4939-9148-8_7","article-title":"Isolation and Characterization of Extracellular Vesicles Derived From Trypanosoma cruzi","volume":"1955","author":"Rossi","year":"2019","journal-title":"Methods Mol Biol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1086\/345882","article-title":"Implication of Transforming Growth Factor\u2013\u03b21 in Chagas Disease Myocardiopathy","volume":"186","author":"Ara\u00fajo-Jorge","year":"2002","journal-title":"J Infect Dis"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12259","article-title":"The Role of Extracellular Vesicles in Plasmodium and Other Protozoan Parasites","volume":"16","author":"Mantel","year":"2014","journal-title":"Cell Microbiol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftx077","article-title":"Microvesicles Released During the Interaction Between Trypanosoma cruzi TcI and TcII Strains and Host Blood Cells Inhibit Complement System and Increase the Infectivity of Metacyclic Forms of Host Cells in a Strain-Independent Process","volume":"75","author":"Wyllie","year":"2017","journal-title":"Pathog Dis"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2018.1463779","article-title":"Proteomic Analysis Reveals Different Composition of Extracellular Vesicles Released by Two Trypanosoma cruzi Strains Associated With Their Distinct Interaction With Host Cells","volume":"7","author":"Ribeiro","year":"2018","journal-title":"J Extracell Vesicles"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12672","article-title":"Dynamic Flux of Microvesicles Modulate Parasite-Host Cell Interaction of Trypanosoma cruzi in Eukaryotic Cells","volume":"19","author":"Ramirez","year":"2017","journal-title":"Cell Microbiol"},{"key":"B117","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.micinf.2008.10.003","article-title":"Trypanosoma cruzi: Parasite Shed Vesicles Increase Heart Parasitism and Generate an Intense Inflammatory Response","volume":"11","author":"Trocoli Torrecilhas","year":"2009","journal-title":"Microbes Infect"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1021\/pr300947g","article-title":"Proteomic Analysis of Trypanosoma cruzi Secretome: Characterization of Two Populations of Extracellular Vesicles and Soluble Proteins","volume":"12","author":"Bayer-Santos","year":"2013","journal-title":"J Proteome Res"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.2693","article-title":"Mining SNPs in Extracellular Vesicular Transcriptome of Trypanosoma cruzi: A Step Closer to Early Diagnosis of Neglected Chagas Disease","volume":"4","author":"Gaur","year":"2016","journal-title":"PeerJ"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1586\/erv.12.85","article-title":"Accelerating the Development of a Therapeutic Vaccine for Human Chagas Disease: Rationale and Prospects","volume":"11","author":"Dumonteil","year":"2012","journal-title":"Expert Rev Vaccines"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.789145\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T15:49:48Z","timestamp":1674056988000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.789145\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,16]]},"references-count":120,"alternative-id":["10.3389\/fimmu.2021.789145"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.789145","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,16]]},"article-number":"789145"}}