Immunostimulatory Flagellin from <i>Burkholderia pseudomallei</i> Effects on an Increase in the Intracellular Calcium Concentration and Up‐Regulation of TNF‐α by Mononuclear Cells

Chen, Ya Lei; Chen, Yao Shen; Lin, Hsi Hsun; Chan, Chun Wen; Chen, Ssu Ching; Chen, Ching Hsein

doi:10.1111/j.1348-0421.2007.tb03893.x

Cited by 12 publications

(6 citation statements)

References 30 publications

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“…The present study confirmed the previous studies that flagellin is a component of B . pseudomallei that activates human innate and adaptive immune responses [ 8 , 25 – 27 ]. Our observation that rFliC activated HEK-Blue TM -hTLR5 cells confirmed that B .…”

Section: Discussionmentioning

confidence: 99%

Immune response to recombinant Burkholderia pseudomallei FliC

et al. 2018

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Burkholderia pseudomallei is a flagellated Gram-negative bacterium which is the causative agent of melioidosis. The disease poses a major public health problem in tropical regions and diabetes is a major risk factor. The high mortality rate of melioidosis is associated with severe sepsis which involves the overwhelming production of pro-inflammatory cytokines. Bacterial flagellar protein (flagellin) activates Toll-like receptor 5 (TLR5)-mediated innate immune signaling pathways and induces adaptive immune response. However, previous studies of TLR5 signaling in melioidosis have been performed using recombinant flagellin from Salmonella Typhimurium instead of B. pseudomallei. This study aimed to investigate human innate immune response and antibody response against a recombinant B. pseudomallei flagellin (rFliC). We prepared B. pseudomallei rFliC and used it to stimulate HEK-BlueTM-hTLR5 and THP1-DualTM cells to assess TLR5 activation. Subsequently, whole blood stimulation assays with rFliC were performed ex vivo. TLR5-flagellin interactions trigger activation of transcription factor NF-κB in HEK-BlueTM-hTLR5 cells. Pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) productions from whole blood in response to rFliC differed between fourteen healthy individuals. The levels of these cytokines changed in a dose and time-dependent manner. ELISA was used to determine rFliC-specific antibodies in serum samples from different groups of melioidosis patients and healthy subjects. IgG antibody to rFliC in melioidosis patients with diabetes were higher compared with non-diabetic patients. Our results show that B. pseudomallei flagellin is a potent immune stimulator and that the immune responses to rFliC are different among individuals. This may provide valuable insights toward the potential use of rFliC in vaccine development.

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Section: Discussionmentioning

confidence: 99%

Immune response to recombinant Burkholderia pseudomallei FliC

et al. 2018

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“…Other cardiovascular medications are also known to influence the (innate) immune response. For example, certain calcium channel blockers were observed to interfere with both flagellin and LPS signalling [ 26 , 27 ]. Statins and aspirin demonstrate similar anti-inflammatory properties [ 28 – 30 ].…”

Section: Discussionmentioning

confidence: 99%

MDCO-216 Does Not Induce Adverse Immunostimulation, in Contrast to Its Predecessor ETC-216

Reijers

Kallend²,

Malone

et al. 2017

Cardiovasc Drugs Ther

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PurposeAim of this study was to demonstrate that MDCO-216 (human recombinant Apolipoprotein A-I Milano) does not induce adverse immunostimulation, in contrast to its predecessor, ETC-216, which was thought to contain host cell proteins (HCPs) that elicited an inflammatory reaction.MethodsData were taken from a clinical trial in which 24 healthy volunteers (HV) and 24 patients with proven stable coronary artery disease (sCAD) received a single intravenous dose of MDCO-216, ranging 5–40 mg/kg. Additionally, whole blood from 35 HV, 35 sCAD patients and 35 patients requiring acute coronary intervention (aCAD group) was stimulated ex vivo with MDCO-216 and ETC-216.ResultsNo inflammatory reaction was observed in HV and sCAD patients following MDCO-216 treatment, judging by body temperature, white cell counts, neutrophil counts, C-reactive protein, circulating cytokines (IL-6, TNF-α), and adverse events. In the ex vivo experiment, the geometric means (SD) of the ratio of MDCO-216 stimulated IL-6 over background levels were 0.8 (1.9), 0.7 (1.5), 1.0 (2.0) for respectively HV, sCAD, aCAD. The corresponding ETC-216 stimulated values were 15.8 (2.9), 9.5 (3.6), 3.8 (4.0). TNF-α results were comparable. Because many ETC-216 stimulated samples had cytokine concentrations >ULOQ, ratios were categorised and marginal homogeneity of the contingency table (MDCO-216 versus ETC-216) was assessed with the Stuart-Maxwell test. P-values were ≤0.0005 for all populations.ConclusionsMDCO-216 did not induce adverse immunostimulation in HV and sCAD patients, in contrast to ETC-216. Results from the ex vivo stimulation suggests the same holds true for aCAD patients.

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“…They suggested that Ca2 + signalling has a positive effect not only on the maturation of DCs, but also on the functions of DCs such as IL-12 secretion. These reports also suggest that the L-type Ca2 + channel exists in immature monocyte-derived DCs (iMDDCs), supported by the report that the L-type Ca channel exists in human peripheral blood mononuclear cells [22]. However, Faries et al showed that calcium signalling antagonized IL-12 production selectively from immature DCs activated with interferon (IFN)-g, tumour necrosis factor (TNF)-a and soluble CD40 ligand [23].…”

Section: Introductionmentioning

confidence: 71%