Characterisation of secretome-based immune responses of human leukocytes infected with various Mycobacterium tuberculosis lineages

Benjawan Kaewseekhao; Sittiruk Roytrakul; Yodying Yingchutrakul; Marut Laohaviroj; Kanin Salao; Kiatichai Faksri

doi:10.7717/peerj.11565

Characterisation of secretome-based immune responses of human leukocytes infected with various Mycobacterium tuberculosis lineages

PeerJ. 2021 Jun 3:9:e11565. doi: 10.7717/peerj.11565. eCollection 2021.

Authors

Benjawan Kaewseekhao^{1

2}, Sittiruk Roytrakul³, Yodying Yingchutrakul³, Marut Laohaviroj¹, Kanin Salao¹, Kiatichai Faksri^{1

2}

Affiliations

¹ Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
² Research and Diagnostic Center for Emerging Infectious Diseases (RCEID), Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
³ National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, Thailand.

Abstract

Background: Differences in immune responses against different lineages of Mycobacterium tuberculosis (Mtb), and by different types of immune cell, are still poorly understood. We aimed to compare the secretome-based immune responses among three Mtb lineages and among immune-cell types. The immune responses were also investigated during infection and when the bacilli had been eliminated from the immune cells.

Methods: Human primary leukocytes were infected with strains representing three lineages of Mtb (East-Asian, Indo-Oceanic and Euro-American). Label-free GeLC MS/MS proteomic analysis of secretomes was performed. The response of each immune-cell type was compared with the appropriate interactome database for each.

Results: The expression pattern of proteins secreted by Mtb-infected leukocytes differed among Mtb lineages. The ancestral lineage (IO lineage) had a greater ability to activate MMP14 (associated with leukocyte migration) than did the more recent lineages (EA and EuA). During infection, proteins secreted by macrophages, dendritic cells, neutrophils and B-cells were associated with cell proliferation. Following clearance of Mtb, proteins associated with interferon signaling were found in macrophages, dendritic cells and neutrophils: proteins associated with antigen processing were found in B-cells and regulatory T-cells. Expression of immune response-related proteins from many immune-cell types might be suppressed by Mtb infection. Our study has provided a better insight into the host-pathogen interaction and immune response against different Mtb lineages.

Keywords: East-Asian lineage; Euro-American lineage; Indo-Oceanic lineage; Mycobacterium tuberculosis; Proteomics.

Grants and funding

This work was supported by Research and Diagnostic Center for Emerging Infectious Diseases (RCEID) and received scholarship under the Post-Doctoral Training Program from Khon Kaen University, Thailand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.