alpha sub(v) beta sub(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 alpha sub(v) beta sub(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 interac...

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Bibliographic Details
Published in:Infection and immunity 2000-10, Vol.68 (10), p.5673-5678
Main Authors: Dellacasagrande, J, Ghigo, E, Hammami, SM-E, Toman, R, Raoult, D, Capo, C, Mege, J-L
Format: Article
Language:English
Subjects:
Coxiella burnetii
integrins
lipopolysaccharides
tumor necrosis factor-^a
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Summary:Coxiella burnetii, the agent of Q fever, enters human monocytes through alpha sub(v) beta sub(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 alpha sub(v) beta sub(3) integrin was involved in TNF synthesis since peptides containing RGD sequences and blocking antibodies against alpha sub(v) beta sub(3) integrin inhibited TNF transcripts induced by C. burnetii. Nevertheless, the cross-linking of alpha sub(v) beta sub(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 alpha sub(v) beta sub(3) integrin enables surface LPS to stimulate TNF production in THP-1 monocytes.
ISSN:0019-9567