RNA-Seq Revealed Expression of Many Novel Genes Associated With Leishmania donovani Persistence and Clearance in the Host Macrophage
Host- as well as parasite-specific factors are equally crucial in allowing either the parasites to dominate, or host macrophages to resist infection. To identify such factors, we infected murine peritoneal macrophages with either the virulent (vAG83) or the non-virulent (nvAG83) parasites of . Then,...
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Published in | Frontiers in cellular and infection microbiology Vol. 9; p. 17 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
Frontiers Media S.A
05.02.2019
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Subjects | |
Online Access | Get full text |
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Summary: | Host- as well as parasite-specific factors are equally crucial in allowing either the
parasites to dominate, or host macrophages to resist infection. To identify such factors, we infected murine peritoneal macrophages with either the virulent (vAG83) or the non-virulent (nvAG83) parasites of
. Then, through dual RNA-seq, we simultaneously elucidated the transcriptomic changes occurring both in the host and the parasites. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the differentially expressed (DE) genes, we showed that the vAG83-infected macrophages exhibit biased anti-inflammatory responses compared to the macrophages infected with the nvAG83. Moreover, the vAG83-infected macrophages displayed suppression of many important cellular processes, including protein synthesis. Further, through protein-protein interaction study, we showed significant downregulation in the expression of many hubs and hub-bottleneck genes in macrophages infected with vAG83 as compared to nvAG83. Cell signaling study showed that these two parasites activated the MAPK and PI3K-AKT signaling pathways differentially in the host cells. Through gene ontology analyses of the parasite-specific genes, we discovered that the genes for virulent factors and parasite survival were significantly upregulated in the intracellular amastigotes of vAG83. In contrast, genes involved in the immune stimulations, and those involved in negative regulation of the cell cycle and transcriptional regulation, were upregulated in the nvAG83. Collectively, these results depicted a differential regulation in the host and the parasite-specific molecules during
persistence and clearance of the parasites. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Mohammad Asad, Department of Dermatology, School of Medicine, University of Alabama, Birmingham, AL, United States Present Address: Mohammad Shadab, Department of Dermatology, School of Medicine, University of Alabama, Birmingham, AL, United States Edited by: Brice Rotureau, Institut Pasteur, France Roma Sinha, Infection, Immunity and Metabolism Group, Translational Research Institute, mater Research Institute and The University of Queensland, Brisbane, QLD, Australia Reviewed by: Joel Barratt, University of Technology Sydney, Australia; Carlos Robello, Institut Pasteur de Montevideo, Uruguay This article was submitted to Parasite and Host, a section of the journal Frontiers in Cellular and Infection Microbiology Baijayanti Jha, Department of Biochemistry, University of Lausanne, Epalinges, Switzerland |
ISSN: | 2235-2988 2235-2988 |
DOI: | 10.3389/fcimb.2019.00017 |