Differential Toll-Like Receptor-Signalling of Burkholderia pseudomallei Lipopolysaccharide in Murine and Human Models

Weehuizen, Tassili A. F.; Prior, Joann L.; Vaart, Thomas W. van der; Ngugi, Sarah A.; Nepogodiev, Sergey A.; Field, Robert A.; Kager, Liesbeth M.; Veer, Cornelis van ’t; Vos, Alex F. de; Wiersinga, W. Joost

doi:10.1371/journal.pone.0145397

Cited by 20 publications

(27 citation statements)

References 54 publications

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“…We agree with the finding of others that the O-antigens of B. multivorans contribute to TLR4/MD2-mediated signaling and consequently lead to production of high concentrations of inflammatory cytokines (44). Furthermore, the unique acyl 2-hydroxytetradecanoic acid in lipid A from B. pseudomallei LPS or the Ara4N substitution in the core sugars of B. cenocepacia LPS decrease the degree to which the CD14-TLR4-MD2 interaction is achieved (4,20,45). When we compared the genome-related strains, we found that exposure to B.…”

Section: Discussionsupporting

confidence: 92%

A comparison of the immunological potency of Burkholderia lipopolysaccharides in endotoxemic BALB/c mice

Hsueh

Liu

Wang

et al. 2016

Microbiology and Immunology

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Lipopolysaccharide is one of the virulence factors of the soil-borne pathogens Burkholderia pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans, which cause septic melioidosis (often in B. pseudomallei infections but rarely in B. thailandensis infections) or cepacia syndromes (commonly in B. cenocepacia infections but rarely in B. multivorans infections). The inflammatory responses in Burkholderia LPS-induced endotoxemia were evaluated in this study. Prior to induction, the conserved structures and functions of each purified LPS were determined using electrophoretic phenotypes, the ratios of 3-hydroxytetradecanoic to 3-hydroxyhexadecanoic acid and endotoxin units. In an in vitro assay, cytokine expression of myeloid differentiation primary response gene 88 and Toll/IL-1 receptor domain containing adapter-inducing INF-β-dependent signaling-dependent signaling differed when stimulated by different LPS. Endotoxemia was induced in mice by s.c. injection as evidenced by increasing serum concentrations of 3-hydroxytetradecanoic acid and the septic prognostic markers CD62E and ICAM-1. During endotoxemia, splenic CD11b I-A , CD11b CD80 , CD11b CD86 and CD11b CD11c subpopulations increased. After induction with B. pseudomallei LPS, there were significant increases in splenic CD49b NK cells and CD14 macrophages. The inflamed CD11b CCR2 , CD11b CD31 , CD11b CD14 , resident CD11b CX CR1 and progenitor CD11b CD34 cells showed delayed increases in bone marrow. B. multivorans LPS was the most potent inducer of serum cytokines and chemokines, whereas B. cenocepacia LPS induced relatively low concentrations of the chemokines MIP-1α and MIP-1β. Endotoxin activities did not correlate with the virulence of Burkholderia strains. Thus factors other than LPS and/or other mechanisms of low activity LPS must mediate the pathogenicity of highly virulent Burkholderia strains.

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Section: Discussionsupporting

confidence: 92%

A comparison of the immunological potency of Burkholderia lipopolysaccharides in endotoxemic BALB/c mice

Hsueh

Liu

Wang

et al. 2016

Microbiology and Immunology

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“…The deacylation of Y. pestis and F. tularensis lipid A at human body temperature exemplifies a pathoadaptive capacity. Tetra-acylated lipid A is frequently observed in lipid A isolated from B. mallei , B. pseudomallei , and B. thailandensis ( 30 , 42 , 43 ) alongside penta-acylated lipid A, so it is likely that a pagL homologue exists in B. pseudomallei to enzymatically modify the parental penta-acylated lipid A ( Fig. 1 ).…”

Section: Introductionmentioning

confidence: 99%

“…The structure was reproduced from Kawasaki et al ( 40 ) and Gibbons et al ( 52 ). (B) Current B. pseudomallei lipid A structure from the literature, with assumed PagL and LpxO modifications ( 30 , 33 , 43 , 51 ). Carbon lengths of acyl chains are indicated below each chain.…”

Section: Introductionmentioning

confidence: 99%

Lipid A Remodeling Is a Pathoadaptive Mechanism That Impacts Lipopolysaccharide Recognition and Intracellular Survival of Burkholderia pseudomallei

et al. 2018

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“…Several studies have suggested that TLR’s play a significant role in host susceptibility to melioidosis [13, 16–18]. A broader study to determine TLR receptor expression and signaling pathways could provide insights for understanding disease susceptibility and progression following B .…”

Section: Introductionmentioning

confidence: 99%

Host gene expression analysis in Sri Lankan melioidosis patients

et al. 2017

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BackgroundMelioidosis is a life threatening infectious disease caused by the gram-negative bacillus Burkholderia pseudomallei predominantly found in southeast Asia and northern Australia. Studying the host transcription profiles in response to infection is crucial for understanding disease pathogenesis and correlates of disease severity, which may help improve therapeutic intervention and survival. The aim of this study was to analyze gene expression levels of human host factors in melioidosis patients and establish useful correlation with disease biomarkers, compared to healthy individuals and patients with sepsis caused by other pathogens.MethodsThe study population consisted of 30 melioidosis cases, 10 healthy controls and 10 sepsis cases caused by other pathogens. Total RNA was extracted from peripheral blood mononuclear cells (PBMC’s) of study subjects. Gene expression profiles of 25 gene targets including 19 immune response genes and 6 epigenetic factors were analyzed by real time quantitative polymerase chain reaction (RT-qPCR).Principal findingsInflammatory response genes; TLR4, late onset inflammatory mediator HMGB1, genes associated with antigen presentation; MICB, PSMB2, PSMB8, PSME2, epigenetic regulators; DNMT3B, HDAC1, HDAC2 were significantly down regulated, whereas the anti-inflammatory gene; IL4 was up regulated in melioidosis patients compared to sepsis cases caused by other pathogens. Septicaemic melioidosis cases showed significant down regulation of IL8 compared to sepsis cases caused by other pathogens. HMGB1, MICB, PSMB8, PSMB2, PSME2, HDAC1, HDAC2 and DNMT3B showed consistent down regulation of gene expression in melioidosis patients compared to other sepsis infection, irrespective of comorbidities such as diabetes, duration of clinical symptoms and antibiotic treatment.SignificanceSpecific immune response genes and epigenetic regulators are differentially expressed among melioidosis patients and patients with sepsis caused by other pathogens. Therefore, these genes may serve as biomarkers for disease diagnosis to distinguish melioidosis from cases of sepsis due to other infections and therapeutic intervention for melioidosis.

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Differential Toll-Like Receptor-Signalling of Burkholderia pseudomallei Lipopolysaccharide in Murine and Human Models

Cited by 20 publications

References 54 publications

A comparison of the immunological potency of Burkholderia lipopolysaccharides in endotoxemic BALB/c mice

A comparison of the immunological potency of Burkholderia lipopolysaccharides in endotoxemic BALB/c mice

Lipid A Remodeling Is a Pathoadaptive Mechanism That Impacts Lipopolysaccharide Recognition and Intracellular Survival of Burkholderia pseudomallei

Host gene expression analysis in Sri Lankan melioidosis patients

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