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2 results on '"Tassili A. F. Weehuizen"'

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

Author

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

Subjects
Medicine, Science
Abstract

The Gram-negative bacterium Burkholderia pseudomallei causes melioidosis and is a CDC category B bioterrorism agent. Toll-like receptor (TLR)-2 impairs host defense during pulmonary B.pseudomallei infection while TLR4 only has limited impact. We investigated the role of TLRs in B.pseudomallei-lipopolysaccharide (LPS) induced inflammation. Purified B.pseudomallei-LPS activated only TLR2-transfected-HEK-cells during short stimulation but both HEK-TLR2 and HEK-TLR4-cells after 24 h. In human blood, an additive effect of TLR2 on TLR4-mediated signalling induced by B.pseudomallei-LPS was observed. In contrast, murine peritoneal macrophages recognized B.pseudomallei-LPS solely through TLR4. Intranasal inoculation of B.pseudomallei-LPS showed that both TLR4-knockout(-/-) and TLR2x4-/-, but not TLR2-/- mice, displayed diminished cytokine responses and neutrophil influx compared to wild-type controls. These data suggest that B.pseudomallei-LPS signalling occurs solely through murine TLR4, while in human models TLR2 plays an additional role, highlighting important differences between specificity of human and murine models that may have important consequences for B.pseudomallei-LPS sensing by TLRs and subsequent susceptibility to melioidosis.

Published
2015
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2. Differential Toll-Like Receptor-Signalling of Burkholderia pseudomallei Lipopolysaccharide in Murine and Human Models

Author

Sergey A. Nepogodiev, Liesbeth M. Kager, Sarah A. Ngugi, Joann L. Prior, W. Joost Wiersinga, Cornelis van 't Veer, Thomas W. van der Vaart, Tassili A. F. Weehuizen, Robert A. Field, Alex F. de Vos, Other departments, Amsterdam institute for Infection and Immunity, Gastroenterology and Hepatology, Amsterdam Cardiovascular Sciences, Infectious diseases, and Center of Experimental and Molecular Medicine

Subjects
Lipopolysaccharides, Melioidosis, Burkholderia pseudomallei, Lipopolysaccharide, Virulence Factors, medicine.medical_treatment, lcsh:Medicine, Inflammation, Microbiology, chemistry.chemical_compound, medicine, Pneumonia, Bacterial, Animals, Humans, lcsh:Science, Toll-like receptor, Multidisciplinary, biology, lcsh:R, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, medicine.disease, bacterial infections and mycoses, Mice, Mutant Strains, Toll-Like Receptor 2, Mice, Inbred C57BL, Toll-Like Receptor 4, TLR2, Cytokine, HEK293 Cells, chemistry, Immunology, Host-Pathogen Interactions, TLR4, bacteria, lipids (amino acids, peptides, and proteins), lcsh:Q, medicine.symptom, Research Article, Signal Transduction
Abstract

The Gram-negative bacterium Burkholderia pseudomallei causes melioidosis and is a CDC category B bioterrorism agent. Toll-like receptor (TLR)-2 impairs host defense during pulmonary B.pseudomallei infection while TLR4 only has limited impact. We investigated the role of TLRs in B.pseudomallei-lipopolysaccharide (LPS) induced inflammation. Purified B.pseudomallei-LPS activated only TLR2-transfected-HEK-cells during short stimulation but both HEK-TLR2 and HEK-TLR4-cells after 24 h. In human blood, an additive effect of TLR2 on TLR4-mediated signalling induced by B.pseudomallei-LPS was observed. In contrast, murine peritoneal macrophages recognized B.pseudomallei-LPS solely through TLR4. Intranasal inoculation of B.pseudomallei-LPS showed that both TLR4-knockout(-/-) and TLR2x4-/-, but not TLR2-/- mice, displayed diminished cytokine responses and neutrophil influx compared to wild-type controls. These data suggest that B.pseudomallei-LPS signalling occurs solely through murine TLR4, while in human models TLR2 plays an additional role, highlighting important differences between specificity of human and murine models that may have important consequences for B.pseudomallei-LPS sensing by TLRs and subsequent susceptibility to melioidosis.

Published
2015

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