Systemic Lupus Erythematosus Associated With Acute Cytomegalovirus Infection

Summary Macrophages contribute to host defense and to the maintenance of immune homeostasis. On the other hand, they are important targets of human cytomegalovirus (HCMV), a herpesvirus that has evolved many strategies to modulate the host immune response. Since an efficient macrophage trafficking is required for triggering an adequate immune response, we investigated the effects exerted by HCMV infection on macrophage migratory properties. By using endotheliotropic strains of HCMV, we obtained high rates of productively infected human monocyte-derived macrophages (MDM). Twenty-four hours after infection, MDM showed reduced polar morphology and became unable to migrate in response to inflammatory and lymphoid chemokines, bacterial products and growth factors, despite being viable and metabolically active. While chemotactic receptors were partially downregulated on the surface of infected MDM, HCMV induced a dramatic reorganization of the cytoskeleton characterized by rupture of the microtubular network, stiffness of the actin fibers and collapse of the podosomes. Furthermore, supernatants harvested from infected MDM contained high amounts of macrophage migration inhibitory factor (MIF) and were capable to block the migration of uninfected macrophages. Since the immunodepletion of MIF completely restored MDM chemotaxis, we could prove that MIF was indeed responsible for the reduced cell migration. In conclusion, these findings reveal that HCMV employs different mechanisms in order to interfere with movement and positioning of macrophages, possibly leading to an impairment of antiviral responses and to an enhancement of the local inflammation.

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Systemic Lupus Erythematosus Associated With Acute Cytomegalovirus Infection

Cited by 3 publications

References 11 publications

Pathogenetic consequences of cytomegalovirus-host co-evolution

Pathogenetic consequences of cytomegalovirus-host co-evolution

Pathophysiology and Clinical Spectrum of Infections in Systemic Lupus Erythematosus

Human Cytomegalovirus Paralyzes Macrophage Motility through Down-Regulation of Chemokine Receptors, Reorganization of the Cytoskeleton, and Release of Macrophage Migration Inhibitory Factor

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