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α(v)β(3) Integrin and Bacterial Lipopolysaccharide Are Involved in Coxiella burnetii-Stimulated Production of Tumor Necrosis Factor by Human Monocytes

Coxiella burnetii, the agent of Q fever, enters human monocytes through α(v)β(3) integrin and survives inside host cells. In addition, C. burnetii stimulates the synthesis of inflammatory cytokines including tumor necrosis factor (TNF) by monocytes. We studied the role of the interaction of C. burne...

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Main Authors: Dellacasagrande, Jérôme, Ghigo, Eric, Machergui-El , Sarah, Hammami, Toman, Rudolf, Raoult, Didier, Capo, Christian, Mege, Jean-Louis
Formato: Artigo
Idioma:en
Publicado em: American Society for Microbiology 2000
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Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC101522/
https://ncbi.nlm.nih.gov/pubmed/10992470
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spelling pubmed-1015222002-09-12 α(v)β(3) Integrin and Bacterial Lipopolysaccharide Are Involved in Coxiella burnetii-Stimulated Production of Tumor Necrosis Factor by Human Monocytes Dellacasagrande, Jérôme Ghigo, Eric Machergui-El , Sarah Hammami Toman, Rudolf Raoult, Didier Capo, Christian Mege, Jean-Louis Infect Immun Host Response and Inflammation Coxiella burnetii, the agent of Q fever, enters human monocytes through α(v)β(3) integrin and survives inside host cells. In addition, C. burnetii stimulates the synthesis of inflammatory cytokines including tumor necrosis factor (TNF) by monocytes. We studied the role of the interaction of C. burnetii with THP-1 monocytes in TNF production. TNF transcripts and TNF release reached maximum values within 4 h. Almost all monocytes bound C. burnetii after 4 h, while the percentage of phagocytosing monocytes did not exceed 20%. Cytochalasin D, which prevented the uptake of C. burnetii without interfering with its binding, did not affect the expression of TNF mRNA. Thus, bacterial adherence, but not phagocytosis, is necessary for TNF production by monocytes. The monocyte α(v)β(3) integrin was involved in TNF synthesis since peptides containing RGD sequences and blocking antibodies against α(v)β(3) integrin inhibited TNF transcripts induced by C. burnetii. Nevertheless, the cross-linking of α(v)β(3) integrin by specific antibodies was not sufficient to induce TNF synthesis. The signal delivered by C. burnetii was triggered by bacterial lipopolysaccharide (LPS). Polymyxin B inhibited the TNF production stimulated by C. burnetii, and soluble LPS isolated from C. burnetii largely mimicked viable bacteria. On the other hand, avirulent variants of C. burnetii induced TNF production through an increased binding to monocytes rather than through the potency of their LPS. We suggest that the adherence of C. burnetii to monocytes via α(v)β(3) integrin enables surface LPS to stimulate TNF production in THP-1 monocytes. American Society for Microbiology 2000-10 /pmc/articles/PMC101522/ /pubmed/10992470 Text en Copyright © 2000, American Society for Microbiology
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Host Response and Inflammation
spellingShingle Host Response and Inflammation
Dellacasagrande, Jérôme
Ghigo, Eric
Machergui-El , Sarah
Hammami
Toman, Rudolf
Raoult, Didier
Capo, Christian
Mege, Jean-Louis
α(v)β(3) Integrin and Bacterial Lipopolysaccharide Are Involved in Coxiella burnetii-Stimulated Production of Tumor Necrosis Factor by Human Monocytes
description Coxiella burnetii, the agent of Q fever, enters human monocytes through α(v)β(3) integrin and survives inside host cells. In addition, C. burnetii stimulates the synthesis of inflammatory cytokines including tumor necrosis factor (TNF) by monocytes. We studied the role of the interaction of C. burnetii with THP-1 monocytes in TNF production. TNF transcripts and TNF release reached maximum values within 4 h. Almost all monocytes bound C. burnetii after 4 h, while the percentage of phagocytosing monocytes did not exceed 20%. Cytochalasin D, which prevented the uptake of C. burnetii without interfering with its binding, did not affect the expression of TNF mRNA. Thus, bacterial adherence, but not phagocytosis, is necessary for TNF production by monocytes. The monocyte α(v)β(3) integrin was involved in TNF synthesis since peptides containing RGD sequences and blocking antibodies against α(v)β(3) integrin inhibited TNF transcripts induced by C. burnetii. Nevertheless, the cross-linking of α(v)β(3) integrin by specific antibodies was not sufficient to induce TNF synthesis. The signal delivered by C. burnetii was triggered by bacterial lipopolysaccharide (LPS). Polymyxin B inhibited the TNF production stimulated by C. burnetii, and soluble LPS isolated from C. burnetii largely mimicked viable bacteria. On the other hand, avirulent variants of C. burnetii induced TNF production through an increased binding to monocytes rather than through the potency of their LPS. We suggest that the adherence of C. burnetii to monocytes via α(v)β(3) integrin enables surface LPS to stimulate TNF production in THP-1 monocytes.
author Dellacasagrande, Jérôme
Ghigo, Eric
Machergui-El , Sarah
Hammami
Toman, Rudolf
Raoult, Didier
Capo, Christian
Mege, Jean-Louis
author_facet Dellacasagrande, Jérôme
Ghigo, Eric
Machergui-El , Sarah
Hammami
Toman, Rudolf
Raoult, Didier
Capo, Christian
Mege, Jean-Louis
author_sort Dellacasagrande, Jérôme
title α(v)β(3) Integrin and Bacterial Lipopolysaccharide Are Involved in Coxiella burnetii-Stimulated Production of Tumor Necrosis Factor by Human Monocytes
title_short α(v)β(3) Integrin and Bacterial Lipopolysaccharide Are Involved in Coxiella burnetii-Stimulated Production of Tumor Necrosis Factor by Human Monocytes
title_full α(v)β(3) Integrin and Bacterial Lipopolysaccharide Are Involved in Coxiella burnetii-Stimulated Production of Tumor Necrosis Factor by Human Monocytes
title_fullStr α(v)β(3) Integrin and Bacterial Lipopolysaccharide Are Involved in Coxiella burnetii-Stimulated Production of Tumor Necrosis Factor by Human Monocytes
title_full_unstemmed α(v)β(3) Integrin and Bacterial Lipopolysaccharide Are Involved in Coxiella burnetii-Stimulated Production of Tumor Necrosis Factor by Human Monocytes
title_sort α(v)β(3) integrin and bacterial lipopolysaccharide are involved in coxiella burnetii-stimulated production of tumor necrosis factor by human monocytes
publisher American Society for Microbiology
publisher_facet American Society for Microbiology
publishDate 2000
url https://ncbi.nlm.nih.gov/pmc/articles/PMC101522/
https://ncbi.nlm.nih.gov/pubmed/10992470
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