Dataset Information

Quantitative proteomic analysis of simian primary hepatocytes reveals candidate molecular markers for permissiveness to relapsing malaria Plasmodium cynomolgi

ABSTRACT: A major obstacle in deciphering the hepatic stage of the malaria parasite has been the challenges associated with culturing the infected hepatocytes through the entire liver stage cycle, including that of the dormant form known as hypnozoites. Primary hepatocytes lose their specialized functions in long-term in vitro culture. Hepatocyte infection represents the first step for clinically silent infection and development of malaria parasite Plasmodium in the liver. Thus this liver stage is an ideal target for development of novel antimalarial drugs and vaccine. However, drug discovery against Plasmodium liver stage is severely hampered by the poor understanding of host-cell and parasites interactions during the liver stage infection and development. In this study, we have performed tandem mass tags (TMT) labelling based quantitative proteomic analysis in simian primary hepatocytes cultured in three different systems of susceptibility to plasmodium infection. Our results represent the first documentation of potentially essential molecular markers including asialoglycoprotein receptor (ASGPR), apolipoproteins, squalene synthase and scavenger receptor B1 (SR-BI) required for productive infection and full development in relapsing Plasmodium species. The identification of these candidate proteins for constructive infection and development of Plasmodium in malaria paves the way to explore them as therapeutic targets.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Macaca Fascicularis (crab-eating Macaque) (cynomolgus Monkey)

TISSUE(S): Hepatocyte, Cell Culture

SUBMITTER: Bamaprasad Dutta

LAB HEAD: Siu Kwan SZE

PROVIDER: PXD013310 | Pride | 2019-09-02

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	161213_Novartis_MalariaMonky_TMT10_01_A.raw	Raw
	161213_Novartis_MalariaMonky_TMT10_01_B.raw	Raw
	161213_Novartis_MalariaMonky_TMT10_01_C.raw	Raw
	161213_Novartis_MalariaMonky_TMT10_02_A.raw	Raw
	161213_Novartis_MalariaMonky_TMT10_02_B.raw	Raw

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Quantitative Proteomic Analysis of Simian Primary Hepatocytes Reveals Candidate Molecular Markers for Permissiveness to Relapsing Malaria Plasmodium cynomolgi.

Dembele Laurent L Gupta Devendra Kumar DK Dutta Bamaprasad B Chua Adeline C Y ACY Sze Siu Kwan SK Bifani Pablo P

Proteomics 20191001 19

A major obstacle impeding malaria research is the lack of an in vitro system capable of supporting infection through the entire liver stage cycle of the parasite, including that of the dormant forms known as hypnozoites. Primary hepatocytes lose their liver specific functions in long-term in vitro culture. The malaria parasite Plasmodium initiates infection in hepatocyte. This corresponds to the first step of clinically silent infection and development of malaria parasite Plasmodium in the liver ...[more]

PMID: 31444903

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Project description:After entering their mammalian host via the bite of an Anopheles mosquito, Plasmodium sporozoites migrate to the liver where they traverse several hepatocytes before invading the one inside which they will develop and multiply into thousands of merozoites. Although this constitutes an essential step in malaria infection, the requirements of Plasmodium parasites in liver cells and how they use the host cell for their own survival and development are poorly understood. To gain new insights into the molecular host-parasite interactions that take place during malaria liver infection, we have used high-throughput microarray technology to determine the transcriptional profile of P. yoelii-infected hepatocytes that were collected from P. yoelii-infected mice 24 and 40 h after infection. This in vivo microarray expression was compared with the microarray analysis of in vitro infected hepatoma cells infected with closely related rodent malaria parasite P. berghei. Differential expression patterns for host genes identify genes and pathways involved in the host response to rodent Plasmodium parasites. Keywords: gene expression Total RNA from sorted liver stage (LS) infected hepatocytes were isolated from PyGFP-infected BALB/c mice as described in Tarun et al (2008). RNA from LS-infected hepatocytes were isolated at two time points post-infection (pi): 24 hr pi (LS24) and 40 hr pi (LS40). As control, RNA from hepatocytes isolated from mock-infected mice (infected with salivary gland extract) at the same time points was also isolated following the same procedure. Total RNA was then subjected to two rounds of linear amplification using the Amino Allyl Message Amp II aRNA Amplification Kit (Ambion) according to manufaturerâs directions. The quality of total and amplified RNAs were examined with the Agilent 2100 BioanalyzerTM (Agilent Technologies) and the quantity of the RNA samples was assessed using a Nanodrop ND-1000 spectrophotometer prior to microarray hybridization. For each timepoint two independent biological replicates were obtained.