Interleukin-4 induces Coxiella burnetii replication in human monocytes but not in macrophages

Coxiella burnetii, an obligate intracellular bacterium, is the agent of Q fever. The chronic disease is characterized by impaired cell-mediated immune response and microbicidal activity of monocytes. We hypothesized that interleukin(IL)-4, a Th2 cytokine, interferes with the fate of C. burnetii inside monocytes. C. burnetii survived without multiplication in resting monocytes, but replicated in IL-4-treated monocytes. The effect of IL-4 is specific for monocytes since IL-4 did not stimulate C. burnetii replication in monocyte-derived macrophages. The effects of IL-4 on bacterial replication and on tumor necrosis factor (TNF) production in monocytes were apparently not related. Although IL-4 inhibited C. burnetii-stimulated release of TNF, the addition of recombinant TNF to IL-4-treated monocytes did not prevent the IL-4 effect. These results suggest that IL-4 enables monocytes to support C. burnetii replication and a Th2 polarization of immune response that may interfere with immune control of Q fever.