Characterization of Plasmodium vivax Proteins in Plasma-Derived Exosomes From Malaria-Infected Liver-Chimeric Humanized Mice
Exosomes are extracellular vesicles of endocytic origin containing molecular signatures implying the cell of origin; thus, they offer a unique opportunity to discover biomarkers of disease. Plasmodium vivax, responsible for more than half of all malaria cases outside Africa, is a major obstacle in t...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-06-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.01271/full |
| _version_ | 1811302857325936640 |
|---|---|
| author | Melisa Gualdrón-López Melisa Gualdrón-López Erika L. Flannery Niwat Kangwanrangsan Vorada Chuenchob Dietmar Fernandez-Orth Joan Segui-Barber Felix Royo Juan M. Falcón-Pérez Juan M. Falcón-Pérez Juan M. Falcón-Pérez Carmen Fernandez-Becerra Carmen Fernandez-Becerra Marcus V. G. Lacerda Marcus V. G. Lacerda Stefan H. I. Kappe Jetsumon Sattabongkot Juan R. Gonzalez Sebastian A. Mikolajczak Hernando A. del Portillo Hernando A. del Portillo Hernando A. del Portillo |
| author_facet | Melisa Gualdrón-López Melisa Gualdrón-López Erika L. Flannery Niwat Kangwanrangsan Vorada Chuenchob Dietmar Fernandez-Orth Joan Segui-Barber Felix Royo Juan M. Falcón-Pérez Juan M. Falcón-Pérez Juan M. Falcón-Pérez Carmen Fernandez-Becerra Carmen Fernandez-Becerra Marcus V. G. Lacerda Marcus V. G. Lacerda Stefan H. I. Kappe Jetsumon Sattabongkot Juan R. Gonzalez Sebastian A. Mikolajczak Hernando A. del Portillo Hernando A. del Portillo Hernando A. del Portillo |
| author_sort | Melisa Gualdrón-López |
| collection | DOAJ |
| description | Exosomes are extracellular vesicles of endocytic origin containing molecular signatures implying the cell of origin; thus, they offer a unique opportunity to discover biomarkers of disease. Plasmodium vivax, responsible for more than half of all malaria cases outside Africa, is a major obstacle in the goal of malaria elimination due to the presence of dormant liver stages (hypnozoites), which after the initial infection may reactivate to cause disease. Hypnozoite infection is asymptomatic and there are currently no diagnostic tools to detect their presence. The human liver-chimeric (FRG huHep) mouse is a robust P. vivax infection model for exo-erythrocytic development of liver stages, including hypnozoites. We studied the proteome of plasma-derived exosomes isolated from P. vivax infected FRG huHep mice with the objective of identifying liver-stage expressed parasite proteins indicative of infection. Proteomic analysis of these exosomes showed the presence of 290 and 234 proteins from mouse and human origin, respectively, including canonical exosomal markers. Human proteins include proteins previously detected in liver-derived exosomes, highlighting the potential of this chimeric mouse model to study plasma exosomes derived unequivocally from human hepatocytes. Noticeably, we identified 17 parasite proteins including enzymes, surface proteins, components of the endocytic pathway and translation machinery, as well as uncharacterized proteins. Western blot analysis validated the presence of human arginase-I and an uncharacterized P. vivax protein in plasma-derived exosomes. This study represents a proof-of-principle that plasma-derived exosomes from P. vivax infected FRG-huHep mice contain human hepatocyte and P. vivax proteins with the potential to unveil biological features of liver infection and identify biomarkers of hypnozoite infection. |
| first_indexed | 2024-04-13T07:36:51Z |
| format | Article |
| id | doaj.art-580a4f327ad84defa1f7c6e360dd02f1 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T07:36:51Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-580a4f327ad84defa1f7c6e360dd02f12022-12-22T02:56:07ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-06-01910.3389/fmicb.2018.01271364993Characterization of Plasmodium vivax Proteins in Plasma-Derived Exosomes From Malaria-Infected Liver-Chimeric Humanized MiceMelisa Gualdrón-López0Melisa Gualdrón-López1Erika L. Flannery2Niwat Kangwanrangsan3Vorada Chuenchob4Dietmar Fernandez-Orth5Joan Segui-Barber6Felix Royo7Juan M. Falcón-Pérez8Juan M. Falcón-Pérez9Juan M. Falcón-Pérez10Carmen Fernandez-Becerra11Carmen Fernandez-Becerra12Marcus V. G. Lacerda13Marcus V. G. Lacerda14Stefan H. I. Kappe15Jetsumon Sattabongkot16Juan R. Gonzalez17Sebastian A. Mikolajczak18Hernando A. del Portillo19Hernando A. del Portillo20Hernando A. del Portillo21Instituto Salud Global, Hospital Clinic—Universitat de Barcelona, Barcelona, SpainInstitute for Health Sciences Trias I Pujol, Barcelona, SpainCenter for Infectious Disease Research, Seattle, WA, United StatesDepartment of Pathobiology, Faculty of Science, Mahidol University, Bangkok, ThailandCenter for Infectious Disease Research, Seattle, WA, United StatesInstituto Salud Global, Hospital Clinic—Universitat de Barcelona, Barcelona, SpainInstituto Salud Global, Hospital Clinic—Universitat de Barcelona, Barcelona, SpainExosomes Laboratory, CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERHD), Derio, SpainExosomes Laboratory, CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERHD), Derio, SpainMetabolomics platform, CIC bioGUNE, CIBERehd, Derio, SpainIKERBASKE Basque Foundation for Science, Bilbao, SpainInstituto Salud Global, Hospital Clinic—Universitat de Barcelona, Barcelona, SpainInstitute for Health Sciences Trias I Pujol, Barcelona, SpainFundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, BrazilInstituto Leônidas & Maria Deane, Manaus, BrazilCenter for Infectious Disease Research, Seattle, WA, United States0Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandInstituto Salud Global, Hospital Clinic—Universitat de Barcelona, Barcelona, SpainCenter for Infectious Disease Research, Seattle, WA, United StatesInstituto Salud Global, Hospital Clinic—Universitat de Barcelona, Barcelona, SpainInstitute for Health Sciences Trias I Pujol, Barcelona, Spain1Catalan Institution for Research and Advanced Studies, Barcelona, SpainExosomes are extracellular vesicles of endocytic origin containing molecular signatures implying the cell of origin; thus, they offer a unique opportunity to discover biomarkers of disease. Plasmodium vivax, responsible for more than half of all malaria cases outside Africa, is a major obstacle in the goal of malaria elimination due to the presence of dormant liver stages (hypnozoites), which after the initial infection may reactivate to cause disease. Hypnozoite infection is asymptomatic and there are currently no diagnostic tools to detect their presence. The human liver-chimeric (FRG huHep) mouse is a robust P. vivax infection model for exo-erythrocytic development of liver stages, including hypnozoites. We studied the proteome of plasma-derived exosomes isolated from P. vivax infected FRG huHep mice with the objective of identifying liver-stage expressed parasite proteins indicative of infection. Proteomic analysis of these exosomes showed the presence of 290 and 234 proteins from mouse and human origin, respectively, including canonical exosomal markers. Human proteins include proteins previously detected in liver-derived exosomes, highlighting the potential of this chimeric mouse model to study plasma exosomes derived unequivocally from human hepatocytes. Noticeably, we identified 17 parasite proteins including enzymes, surface proteins, components of the endocytic pathway and translation machinery, as well as uncharacterized proteins. Western blot analysis validated the presence of human arginase-I and an uncharacterized P. vivax protein in plasma-derived exosomes. This study represents a proof-of-principle that plasma-derived exosomes from P. vivax infected FRG-huHep mice contain human hepatocyte and P. vivax proteins with the potential to unveil biological features of liver infection and identify biomarkers of hypnozoite infection.https://www.frontiersin.org/article/10.3389/fmicb.2018.01271/fullPlasmodium vivaxhypnozoiteexosomeproteomicsbiomarkerhumanized mice |
| spellingShingle | Melisa Gualdrón-López Melisa Gualdrón-López Erika L. Flannery Niwat Kangwanrangsan Vorada Chuenchob Dietmar Fernandez-Orth Joan Segui-Barber Felix Royo Juan M. Falcón-Pérez Juan M. Falcón-Pérez Juan M. Falcón-Pérez Carmen Fernandez-Becerra Carmen Fernandez-Becerra Marcus V. G. Lacerda Marcus V. G. Lacerda Stefan H. I. Kappe Jetsumon Sattabongkot Juan R. Gonzalez Sebastian A. Mikolajczak Hernando A. del Portillo Hernando A. del Portillo Hernando A. del Portillo Characterization of Plasmodium vivax Proteins in Plasma-Derived Exosomes From Malaria-Infected Liver-Chimeric Humanized Mice Frontiers in Microbiology Plasmodium vivax hypnozoite exosome proteomics biomarker humanized mice |
| title | Characterization of Plasmodium vivax Proteins in Plasma-Derived Exosomes From Malaria-Infected Liver-Chimeric Humanized Mice |
| title_full | Characterization of Plasmodium vivax Proteins in Plasma-Derived Exosomes From Malaria-Infected Liver-Chimeric Humanized Mice |
| title_fullStr | Characterization of Plasmodium vivax Proteins in Plasma-Derived Exosomes From Malaria-Infected Liver-Chimeric Humanized Mice |
| title_full_unstemmed | Characterization of Plasmodium vivax Proteins in Plasma-Derived Exosomes From Malaria-Infected Liver-Chimeric Humanized Mice |
| title_short | Characterization of Plasmodium vivax Proteins in Plasma-Derived Exosomes From Malaria-Infected Liver-Chimeric Humanized Mice |
| title_sort | characterization of plasmodium vivax proteins in plasma derived exosomes from malaria infected liver chimeric humanized mice |
| topic | Plasmodium vivax hypnozoite exosome proteomics biomarker humanized mice |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.01271/full |
| work_keys_str_mv | AT melisagualdronlopez characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT melisagualdronlopez characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT erikalflannery characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT niwatkangwanrangsan characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT voradachuenchob characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT dietmarfernandezorth characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT joanseguibarber characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT felixroyo characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT juanmfalconperez characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT juanmfalconperez characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT juanmfalconperez characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT carmenfernandezbecerra characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT carmenfernandezbecerra characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT marcusvglacerda characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT marcusvglacerda characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT stefanhikappe characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT jetsumonsattabongkot characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT juanrgonzalez characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT sebastianamikolajczak characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT hernandoadelportillo characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT hernandoadelportillo characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice AT hernandoadelportillo characterizationofplasmodiumvivaxproteinsinplasmaderivedexosomesfrommalariainfectedliverchimerichumanizedmice |