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Dual RNA-seq identifies human mucosal immunity protein Mucin-13 as a hallmark of Plasmodium exoerythrocytic infection
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Dual RNA-seq identifies human mucosal immunity protein Mucin-13 as a hallmark of Plasmodium exoerythrocytic infection
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Journal Article
Dual RNA-seq identifies human mucosal immunity protein Mucin-13 as a hallmark of Plasmodium exoerythrocytic infection
2019
Overview
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.
Host-parasite interactions during the exoerythrocytic stage of
Plasmodium
infection remains poorly understood. Using dual RNA-Seq, the authors show that human mucosal immunity protein mucin-13 is upregulated during
Plasmodium
hepatic-stage infection and marks infected cells independent of tested
Plasmodium
species.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/89
/ 14/19
/ 38
/ 45/91
/ Carcinoma, Hepatocellular - immunology
/ Carcinoma, Hepatocellular - parasitology
/ Genomes
/ Hepatoma
/ HSP70 Heat-Shock Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Immunity
/ Immunity, Mucosal - genetics
/ Immunity, Mucosal - physiology
/ Liver Neoplasms - immunology
/ Mucin
/ Plasmodium berghei - pathogenicity
/ Proteins
/ RNA
/ Science
