Dual RNA-seq identifies human mucosal immunity protein Mucin-13 as a hallmark of Plasmodium exoerythrocytic infection

Gregory M. LaMonte, Pamela Orjuela-Sanchez, Jaeson Calla, Lawrence T. Wang, Shangzhong Li, Justine Swann, Annie N. Cowell, Bing Yu Zou, Alyaa M. Abdel-Haleem, Zaira Hellen Villa Galarce, Marta Moreno, Carlos Tong Rios, Joseph M. Vinetz, Nathan Lewis, Elizabeth A. Winzeler

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The exoerythrocytic stage of Plasmodium infection is a critical window for prophylactic intervention. Using genome-wide dual RNA sequencing of flow-sorted infected and uninfected hepatoma cells we show that the human mucosal immunity gene, mucin-13 (MUC13), is strongly upregulated during Plasmodium exoerythrocytic hepatic-stage infection. We confirm MUC13 transcript increases 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, marking both P. berghei and P. vivax infected cells, and that MUC13 can be used to identify compounds that inhibit parasite replication in hepatocytes. This data provides insights into host-parasite interactions in Plasmodium infection, and demonstrates that a component of host mucosal immunity is reprogrammed during the progression of infection.
Original languageEnglish (US)
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Jan 30 2019

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: 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.

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