Open AccessRevealing immune responses in the Mycobacterium avium subsp. paratuberculosis-infected THP-1 cells using single cell RNA-sequencing
Author(s) -
Hong-Tae Park,
Woo Bin Park,
Suji Kim,
Jae Yong Lim,
Gyoungju Nah,
Han Sang Yoo
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0254194
Subject(s) - paratuberculosis , biology , thp1 cell line , immune system , cd14 , cell type , chemokine , cell , transcriptome , single cell analysis , cell culture , immunology , mycobacterium , microbiology and biotechnology , gene expression , gene , genetics , bacteria
Mycobacterium avium subsp. paratuberculosis (MAP) is a causative agent of Johne’s disease, which is a chronic and debilitating disease in ruminants. MAP is also considered to be a possible cause of Crohn’s disease in humans. However, few studies have focused on the interactions between MAP and human macrophages to elucidate the pathogenesis of Crohn’s disease. We sought to determine the initial responses of human THP-1 cells against MAP infection using single-cell RNA-seq analysis. Clustering analysis showed that THP-1 cells were divided into seven different clusters in response to phorbol-12-myristate-13-acetate (PMA) treatment. The characteristics of each cluster were investigated by identifying cluster-specific marker genes. From the results, we found that classically differentiated cells express CD14 , CD36 , and TLR2 , and that this cell type showed the most active responses against MAP infection. The responses included the expression of proinflammatory cytokines and chemokines such as CCL4 , CCL3 , IL1B , IL8 , and CCL20 . In addition, the Mreg cell type, a novel cell type differentiated from THP-1 cells, was discovered. Thus, it is suggested that different cell types arise even when the same cell line is treated under the same conditions. Overall, analyzing gene expression patterns via scRNA-seq classification allows a more detailed observation of the response to infection by each cell type.