Programmed Death Ligand 1 on Burkholderia pseudomallei–Infected Human Polymorphonuclear Neutrophils Impairs T Cell Functions
| Autor: | Surachat Buddhisa, Manabu Ato, Darawan Rinchai, Gregory J. Bancroft, Ganjana Lertmemongkolchai |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Burkholderia pseudomallei Melioidosis Neutrophils T cell Cellular differentiation Programmed Cell Death 1 Receptor Immunology chemical and pharmacologic phenomena Cell Communication B7-H1 Antigen Microbiology Immunomodulation Pathogenesis Immune system T-Lymphocyte Subsets medicine Humans Immunology and Allergy Aged Innate immune system biology Middle Aged biology.organism_classification medicine.disease In vitro medicine.anatomical_structure Diabetes Mellitus Type 2 Female Signal Transduction |
| Zdroj: | The Journal of Immunology. 194:4413-4421 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1402417 |
| Popis: | Polymorphonuclear neutrophils (PMNs) are terminally differentiated cells that are involved in innate immune responses and form an early line of defense against pathogens. More recently, it has been shown that PMNs have immunosuppressive abilities on other immune cells. However, the effect of PMNs on T cell responses during bacterial infection remains to be determined. In this report, we examined the interaction of PMNs and T cells in response to infection with Burkholderia pseudomallei, the causative agent of human melioidosis. We observed that CD4+ T cell proliferation and IFN-γ production in response to polyclonal activators is significantly inhibited by uninfected PMNs, and to a greater extent B. pseudomallei–infected PMNs. Programmed death ligand 1 (PD-L1), a known regulator of T cell activation, is increased in mRNA expression in the blood of patients and upon infection of PMNs in vitro. The increased expression of PD-L1 was correlated with the degree of T cell inhibition in individuals with type 2 diabetes, a major risk factor of melioidosis. In vitro, addition of anti–PD-L1 Abs blocked this inhibitory activity and restored proliferation of CD4+ T cells and IFN-γ production, suggesting that PD-L1 on B. pseudomallei–infected PMNs is a regulatory molecule for the functions of T cells and may be involved in pathogenesis versus control of melioidosis. |
| Databáze: | OpenAIRE |
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