Experimental exposure of Burkholderia pseudomallei crude culture filtrate upregulates PD-1 on T lymphocytes

• Type of Material: Article
• Authors: Nivedita Menon, University of Malaya, Lembah Pantai; Vanitha Mariappan, University of Malaya, Lembah Pantai; Kumutha M Vellasamy, University of Malaya, Lembah Pantai; Chandramathi Samudi, University of Malaya, Lembah Pantai; Jia-Xiang See, University of Malaya, Lembah Pantai; Sankar P Ganesh, Central University of Tamil Nadu; Alireza Saeidi, Emory University; Jamuna Vadivelu, University of Malaya, Lembah Pantai; Esaki Muthu Shankar, University of Malaya, Lembah Pantai
• Language: English
• Date: 2020-02-14
• Publisher: Microbiology Society
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1099/acmi.0.000110
• Title of Journal or Parent Work: Access Microbiology
• Volume: 2
• Issue: 5
• Grant/Funding Information: The authors acknowledge the funding provided by the Ministry of Higher Education (MOHE), Malaysia under the High Impact Research (HIR)-MOHE project (E000013-20001), the Ministry of Science, Innovation and Technology (MOSTI), Malaysia under the Science Fund (55-02-03-1002) and the University of Malaya research grant (RG029-09HTM) titled ‘Immunology of persistent bacterial infections using Burkholderia pseudomallei as a model’ for J. V. and E. M. S.
• Keywords: immune responses; Burkholderia pseudomallei; culture filtrate; PD-1
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Microbiology

Abstract

Burkholderia pseudomallei is the causative agent for melioidosis. Because of its intracellular nature, the bacterium is capable of replicating within a plethora of eukaryotic cell lines. B. pseudomallei can remain dormant within host cells without symptoms for years, causing recrudescent infections. Here, we investigated the pathogenesis mechanism behind the suppression of T cell responses by B. pseudomallei . Peripheral blood mononuclear cells (1×106 cells/well) isolated by Ficoll Paque (Sigma-Aldrich) density gradient centrifugation were incubated with optimized concentrations of bacterial crude culture filtrate antigens (CFAs) (10 ug ml−1) and heat-killed bacteria [1 : 10 multiplicity of infection (m.o.i.)]. Following incubation, cells were investigated for surface expression of coinhibitory molecules by flow cytometry. We found that B. pseudomallei induced the upregulation of programmed death 1 (PD-1), a molecule responsible for T cell exhaustion, on T cells in vitro following exposure to crude CFAs of B. pseudomallei . This upregulation of PD-1 probably contributes to poor immune surveillance and disease pathogenesis.