Defective monocyte dynamics in Q fever granuloma deficiency.

Abstract

The outcome of Q fever, an infectious disease caused by Coxiella burnetii, is associated with granuloma formation. Granulomas are present in patients with resolutive Q fever but are lacking in patients with chronic Q fever. Study of granuloma formation requires invasive approaches. Here, we took advantage of a recently described method that enables in vitro generation of human granulomas specific for C. burnetii. Circulating mononuclear cells progressively accumulated around beads coated with C. burnetii extracts, and complete granulomas were generated in 8 days. Granuloma cells consisted of macrophages, lymphocytes, and, to a lesser extent, epithelioid cells and multinucleated giant cells. Early events that govern granuloma formation were studied using live-imaging microscopy. Monocytes migrated toward C. burnetii-coated beads independently of the presence of T lymphocytes and then recruited T lymphocytes. About 90% of patients with chronic Q fever failed to form granulomas. This deficiency was associated with defective migration of monocytes toward coated beads. Monocytes were involved in the early stages of granuloma formation and recruited T lymphocytes to complete granuloma formation. This article describes a direct relationship between defective granuloma formation and defective migration of monocytes.