αvβ3Integrin and Bacterial Lipopolysaccharide Are Involved inCoxiella burnetii-Stimulated Production of Tumor Necrosis Factor by Human Monocytes

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Abstract
Coxiella burnetii, the agent of Q fever, enters human monocytes through αvβ3integrin and survives inside host cells. In addition,C. burnetiistimulates the synthesis of inflammatory cytokines including tumor necrosis factor (TNF) by monocytes. We studied the role of the interaction ofC. burnetiiwith THP-1 monocytes in TNF production. TNF transcripts and TNF release reached maximum values within 4 h. Almost all monocytes boundC. burnetiiafter 4 h, while the percentage of phagocytosing monocytes did not exceed 20%. Cytochalasin D, which prevented the uptake ofC. burnetiiwithout 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 αvβ3integrin was involved in TNF synthesis since peptides containing RGD sequences and blocking antibodies against αvβ3integrin inhibited TNF transcripts induced byC. burnetii. Nevertheless, the cross-linking of αvβ3integrin by specific antibodies was not sufficient to induce TNF synthesis. The signal delivered byC. burnetiiwas triggered by bacterial lipopolysaccharide (LPS). Polymyxin B inhibited the TNF production stimulated byC. burnetii, and soluble LPS isolated fromC. burnetiilargely mimicked viable bacteria. On the other hand, avirulent variants ofC. burnetiiinduced TNF production through an increased binding to monocytes rather than through the potency of their LPS. We suggest that the adherence ofC. burnetiito monocytes via αvβ3integrin enables surface LPS to stimulate TNF production in THP-1 monocytes.

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