Human Polymorphonuclear Neutrophil Responses to
            <i>Burkholderia pseudomallei</i>
            in Healthy and Diabetic Subjects

Chanchamroen, Sujin; Kewcharoenwong, Chidchamai; Susaengrat, Wattanachai; Ato, Manabu; Lertmemongkolchai, Ganjana

doi:10.1128/iai.00503-08

Cited by 113 publications

(153 citation statements)

References 46 publications

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“…Our previous studies and those of others in diabetes mellitus patients have described defects in PMN phagocytosis, migration, and oxidative burst responses to kill B. pseudomallei (28), as well as reductions in proinflammatory cytokines (40) and dysfunction in Th1 cell responses to B. pseudomallei infection (41). We report in this article that increased PD-L1 expression on B. pseudomallei-infected PMNs correlated with increasing T cell dysfunction in type 2 diabetic patients.…”

Section: Discussionsupporting

confidence: 59%

“…Human PMNs, PBMCs, and CD4 + T cells were isolated from heparinanticoagulated venous blood from healthy and diabetic subjects using the previously reported criteria and methods (28). In brief, PMNs were isolated by 3% Dextran T-500 sedimentation (Amersham) and separated by Ficoll-Hypaque density gradient centrifugation (Sigma Aldrich), PBMCs were collected, followed by hypotonic lysis to removed RBCs, and also isolated by Ficoll-Hypaque density gradient centrifugation.…”

Section: Isolation Of Peripheral Blood Populationsmentioning

confidence: 99%

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Programmed Death Ligand 1 on Burkholderia pseudomallei–Infected Human Polymorphonuclear Neutrophils Impairs T Cell Functions

Buddhisa

Rinchai

Ato

et al. 2015

The Journal of Immunology

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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.

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Section: Discussionsupporting

confidence: 59%

Section: Isolation Of Peripheral Blood Populationsmentioning

confidence: 99%

Programmed Death Ligand 1 on Burkholderia pseudomallei–Infected Human Polymorphonuclear Neutrophils Impairs T Cell Functions

Buddhisa

Rinchai

Ato

et al. 2015

The Journal of Immunology

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“…Human PMNs were isolated from fresh heparinized venous blood from healthy and diabetic subjects using the previously reported criteria and methods (6). Permission was obtained from the Khon Kaen University Ethics Committee for Human Research, number HE470506.…”

Section: Pmn Isolationmentioning

confidence: 99%

“…Previously, we reported the impairment of cellular functions in PMNs from human subjects with diabetes mellitus (6). PMNs from diabetic subjects were therefore compared to PMNs from healthy subjects for their ability to release extracellular DNA in response to PMA stimulation or B. pseudomallei infection.…”

Section: Net Formation Induced By B Pseudomalleimentioning

confidence: 99%

Neutrophil Extracellular Traps Exhibit Antibacterial Activity against Burkholderia pseudomallei and Are Influenced by Bacterial and Host Factors

et al. 2012

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e Burkholderia pseudomallei is the causative pathogen of melioidosis, of which a major predisposing factor is diabetes mellitus. Polymorphonuclear neutrophils (PMNs) kill microbes extracellularly by the release of neutrophil extracellular traps (NETs). PMNs play a key role in the control of melioidosis, but the involvement of NETs in killing of B. pseudomallei remains obscure. Here, we showed that bactericidal NETs were released from human PMNs in response to B. pseudomallei in a dose-and timedependent manner. B. pseudomallei-induced NET formation required NADPH oxidase activation but not phosphatidylinositol-3 kinase, mitogen-activated protein kinases, or Src family kinase signaling pathways. B. pseudomallei mutants defective in the virulence-associated Bsa type III protein secretion system (T3SS) or capsular polysaccharide I (CPS-I) induced elevated levels of NETs. NET induction by such mutants was associated with increased bacterial killing, phagocytosis, and oxidative burst by PMNs. Taken together the data imply that T3SS and the capsule may play a role in evading the induction of NETs. Importantly, PMNs from diabetic subjects released NETs at a lower level than PMNs from healthy subjects. Modulation of NET formation may therefore be associated with the pathogenesis and control of melioidosis.

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“…The strong association between type 2 diabetes and melioidosis presents a unique opportunity to identify, in diabetes, susceptibility factors to infection and disease. No studies have explored the mechanism for increased susceptibility to melioidosis in diabetic patients except for a recent report that found neutrophils isolated from diabetic individuals to be defective in chemotaxis, phagocytosis, and apoptosis toward B. pseudomallei (11).…”

Section: Introductionmentioning

confidence: 99%

Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria

Tan

Lee²,

Low³

et al. 2012

J. Clin. Invest.

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Individuals with type 2 diabetes are at increased risk of acquiring melioidosis, a disease caused by Burkholderia pseudomallei infection. Although up to half of melioidosis patients have underlying diabetes, the mechanisms involved in this increased susceptibility are unknown. We found that B. pseudomallei-infected PBMCs from diabetic patients were impaired in IL-12p70 production, which resulted in decreased IFN-γ induction and poor bacterial killing. The defect was specific to the IL-12-IFN-γ axis. Defective IL-12 production was also observed during Mycobacterium tuberculosis infection, in which diabetes is likewise known to be a strong risk factor. In contrast,

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Human Polymorphonuclear Neutrophil Responses to Burkholderia pseudomallei in Healthy and Diabetic Subjects

Cited by 113 publications

References 46 publications

Programmed Death Ligand 1 on Burkholderia pseudomallei–Infected Human Polymorphonuclear Neutrophils Impairs T Cell Functions

Programmed Death Ligand 1 on Burkholderia pseudomallei–Infected Human Polymorphonuclear Neutrophils Impairs T Cell Functions

Neutrophil Extracellular Traps Exhibit Antibacterial Activity against Burkholderia pseudomallei and Are Influenced by Bacterial and Host Factors

Glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria

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