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

Coxiella burnetii , the agent of Q fever, enters human monocytes through αv β3 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 ofC. burnetii with THP-1 monocytes in TNF production. TNF transcripts and TNF release reached maximum values within 4 h. Almost all monocytes boundC. burnetii after 4 h, while the percentage of phagocytosing monocytes did not exceed 20%. Cytochalasin D, which prevented the uptake ofC. 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 αv β3 integrin was involved in TNF synthesis since peptides containing RGD sequences and blocking antibodies against αv β3 integrin inhibited TNF transcripts induced byC. burnetii . Nevertheless, the cross-linking of αv β3 integrin by specific antibodies was not sufficient to induce TNF synthesis. The signal delivered byC. burnetii was triggered by bacterial lipopolysaccharide (LPS). Polymyxin B inhibited the TNF production stimulated byC. burnetii , and soluble LPS isolated fromC. burnetii largely mimicked viable bacteria. On the other hand, avirulent variants ofC. burnetii induced TNF production through an increased binding to monocytes rather than through the potency of their LPS. We suggest that the adherence ofC. burnetii to monocytes via αv β3 integrin enables surface LPS to stimulate TNF production in THP-1 monocytes.