Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection

Handle URI:
http://hdl.handle.net/10754/625854
Title:
Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection
Authors:
LaMonte, Gregory; Orjuela-Sanchez, Pamela; Wang, Lawrence; Li, Shangzhong; Swann, Justine; Cowell, Annie; Zou, Bing Yu; Abdel- Haleem Mohamed, Alyaa; Villa-Galarce, Zaira; Moreno, Marta; Tong-Rios, Carlos; Vinetz, Joseph; Lewis, Nathan; Winzeler, Elizabeth A
Abstract:
The exoerythrocytic stage of Plasmodium malaria infection is a critical window for prophylactic intervention. Using a genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we identify the human mucosal immunity gene, Mucin13 (MUC13), as strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm that MUC13 expression is upregulated in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, distinguishing both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes across all Human-infecting Plasmodium species. This data presents a novel interface of host-parasite interactions in Plasmodium, in that a component of host mucosal immunity is reprogrammed to assist the progression of infection.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Computational Bioscience Research Center (CBRC)
Citation:
LaMonte G, Orjuela-Sanchez P, Wang L, Li S, Swann J, et al. (2017) Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection. Available: http://dx.doi.org/10.1101/183764.
Publisher:
Cold Spring Harbor Laboratory
Issue Date:
3-Oct-2017
DOI:
10.1101/183764
Type:
Preprint
Sponsors:
We thank the members of the Winzeler and Lewis labs for advice and critical reading of the manuscript. In addition, we thank Medicines for Malaria Venture for all of their support of the insectary in Peru. We would also like to thank the UCSD Institute for Genomic Medicine Sequencing Core Facility and the UCSD Human Embryonic Stem Cell Flow Cytometry Core Facility for their technical support. G.L. is supported by an A.P. Giannini Post-Doctoral Fellowship. E.A.W. is supported by grants from the NIH (5R01AI090141 and R01AI103058). N.E.L. and S.L received funding from the NIGMS (R35 GM119850) and the Novo Nordisk Foundation through the Center for Biosustainability at the Technical University of Denmark (NNF10CC1016517). The P. vivax work was supported by grants to J.M.V from the NIH (D43TW007120 and U19AI089681). A.N.C received support from a NIH T32 AI 007036 training grant.
Additional Links:
https://www.biorxiv.org/content/early/2017/10/02/183764
Appears in Collections:
Other/General Submission; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorLaMonte, Gregoryen
dc.contributor.authorOrjuela-Sanchez, Pamelaen
dc.contributor.authorWang, Lawrenceen
dc.contributor.authorLi, Shangzhongen
dc.contributor.authorSwann, Justineen
dc.contributor.authorCowell, Annieen
dc.contributor.authorZou, Bing Yuen
dc.contributor.authorAbdel- Haleem Mohamed, Alyaaen
dc.contributor.authorVilla-Galarce, Zairaen
dc.contributor.authorMoreno, Martaen
dc.contributor.authorTong-Rios, Carlosen
dc.contributor.authorVinetz, Josephen
dc.contributor.authorLewis, Nathanen
dc.contributor.authorWinzeler, Elizabeth Aen
dc.date.accessioned2017-10-11T12:03:22Z-
dc.date.available2017-10-11T12:03:22Z-
dc.date.issued2017-10-03en
dc.identifier.citationLaMonte G, Orjuela-Sanchez P, Wang L, Li S, Swann J, et al. (2017) Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection. Available: http://dx.doi.org/10.1101/183764.en
dc.identifier.doi10.1101/183764en
dc.identifier.urihttp://hdl.handle.net/10754/625854-
dc.description.abstractThe exoerythrocytic stage of Plasmodium malaria infection is a critical window for prophylactic intervention. Using a genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we identify the human mucosal immunity gene, Mucin13 (MUC13), as strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm that MUC13 expression is upregulated in hepatoma cell lines and primary hepatocytes. In immunofluorescence assays, host MUC13 protein expression distinguishes infected cells from adjacent uninfected cells and shows similar colocalization with parasite biomarkers such as UIS4 and HSP70. We further show that localization patterns are species independent, distinguishing both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes across all Human-infecting Plasmodium species. This data presents a novel interface of host-parasite interactions in Plasmodium, in that a component of host mucosal immunity is reprogrammed to assist the progression of infection.en
dc.description.sponsorshipWe thank the members of the Winzeler and Lewis labs for advice and critical reading of the manuscript. In addition, we thank Medicines for Malaria Venture for all of their support of the insectary in Peru. We would also like to thank the UCSD Institute for Genomic Medicine Sequencing Core Facility and the UCSD Human Embryonic Stem Cell Flow Cytometry Core Facility for their technical support. G.L. is supported by an A.P. Giannini Post-Doctoral Fellowship. E.A.W. is supported by grants from the NIH (5R01AI090141 and R01AI103058). N.E.L. and S.L received funding from the NIGMS (R35 GM119850) and the Novo Nordisk Foundation through the Center for Biosustainability at the Technical University of Denmark (NNF10CC1016517). The P. vivax work was supported by grants to J.M.V from the NIH (D43TW007120 and U19AI089681). A.N.C received support from a NIH T32 AI 007036 training grant.en
dc.publisherCold Spring Harbor Laboratoryen
dc.relation.urlhttps://www.biorxiv.org/content/early/2017/10/02/183764en
dc.rightsArchived with thanks to bioRxiven
dc.subjectMalariaen
dc.subjectbiomarkersen
dc.subjectliver-stage infectionen
dc.subjecthost-pathogen interactionsen
dc.titleDual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infectionen
dc.typePreprinten
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.eprint.versionPre-printen
dc.contributor.institutionDepartment of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United Statesen
dc.contributor.institutionDepartment of Bioengineering, University of California, San Diego, La Jolla, CA 92093, United Statesen
dc.contributor.institutionNovo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, La Jolla, CA 92093, United Statesen
dc.contributor.institutionDivision of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA 92093, United Statesen
dc.contributor.institutionLaboratorio ICEMR-Amazonia, Laboratorio de Investigación y Desarrollo, Facultad de Ciencias y Filosofia, Universidad Peruana Cayetano Heredia, Lima, Peruen
kaust.authorAbdel- Haleem Mohamed, Alyaaen
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