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

Gregory M. LaMonte, Pamela Orjuela-Sanchez, Lawrence Wang, Shangzhong Li, Justine Swann, Annie N. Cowell, Bing Yu Zou, Alyaa M. Abdel-Haleem Mohamed, Zaira Villa-Galarce, Marta Moreno, Carlos Tong-Rios, Joseph M. Vinetz, Nathan Lewis, Elizabeth A. Winzeler
doi: https://doi.org/10.1101/183764
Gregory M. LaMonte
1Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States
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Pamela Orjuela-Sanchez
1Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States
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Lawrence Wang
1Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States
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Shangzhong Li
1Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States
2Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, La Jolla, CA 92093, United States
3Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, United States
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Justine Swann
1Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States
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Annie N. Cowell
4Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA 92093, United States
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Bing Yu Zou
1Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States
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Alyaa M. Abdel-Haleem Mohamed
5Computational Bioscience Research Centre (CBRC) and Biological and Environmental Sciences and Engineering (BESE) division, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia
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Zaira Villa-Galarce
6Laboratorio ICEMR-Amazonia, Laboratorio de Investigación y Desarrollo, Facultad de Ciencias y Filosofia, Universidad Peruana Cayetano Heredia, Lima, Peru
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Marta Moreno
6Laboratorio ICEMR-Amazonia, Laboratorio de Investigación y Desarrollo, Facultad de Ciencias y Filosofia, Universidad Peruana Cayetano Heredia, Lima, Peru
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Carlos Tong-Rios
6Laboratorio ICEMR-Amazonia, Laboratorio de Investigación y Desarrollo, Facultad de Ciencias y Filosofia, Universidad Peruana Cayetano Heredia, Lima, Peru
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Joseph M. Vinetz
4Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA 92093, United States
6Laboratorio ICEMR-Amazonia, Laboratorio de Investigación y Desarrollo, Facultad de Ciencias y Filosofia, Universidad Peruana Cayetano Heredia, Lima, Peru
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Nathan Lewis
1Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States
2Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, La Jolla, CA 92093, United States
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Elizabeth A. Winzeler
1Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, CA 92093, United States
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Summary

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.

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Posted October 02, 2017.
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Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection
Gregory M. LaMonte, Pamela Orjuela-Sanchez, Lawrence Wang, Shangzhong Li, Justine Swann, Annie N. Cowell, Bing Yu Zou, Alyaa M. Abdel-Haleem Mohamed, Zaira Villa-Galarce, Marta Moreno, Carlos Tong-Rios, Joseph M. Vinetz, Nathan Lewis, Elizabeth A. Winzeler
bioRxiv 183764; doi: https://doi.org/10.1101/183764
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Dual RNAseq shows the human mucosal immunity protein, MUC13, is a hallmark of Plasmodium exoerythrocytic infection
Gregory M. LaMonte, Pamela Orjuela-Sanchez, Lawrence Wang, Shangzhong Li, Justine Swann, Annie N. Cowell, Bing Yu Zou, Alyaa M. Abdel-Haleem Mohamed, Zaira Villa-Galarce, Marta Moreno, Carlos Tong-Rios, Joseph M. Vinetz, Nathan Lewis, Elizabeth A. Winzeler
bioRxiv 183764; doi: https://doi.org/10.1101/183764

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