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

• 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
• Journal Title: Access Microbiology
• Volume: Volume 2, Number 5
• Publisher: Microbiology Society | 2020-02-14
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1099/acmi.0.000110
• Subjects: Biology, Microbiology; Health Sciences, Medicine and Surgery
• Keywords: Burkholderia pseudomallei; PD-1; culture filtrate; immune responses

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.