Molecular Mechanisms of Borrelia burgdorferi Phagocytosis and Intracellular Processing by Human Macrophages

SIMPLE SUMMARY: Borreliae are a group of highly motile bacteria that are characterized by their corkscrew-like shape. They can be transferred by a tick bite to a human host and cause severe illnesses. Accordingly, an untreated infection with Borrelia burgdorferi can lead to the development of Lyme disease, which can affect the skin, joints, heart and nervous system. It is thus important to understand how borreliae interact with the human immune system, and which mechanisms lead to their depletion in the human body. Macrophages are part of the innate immune system and among the first cells that encounter invading borreliae. In this review, we discuss the molecular mechanisms that enable macrophages to recognize, take up and digest borreliae. We also point out potential ways in which borreliae might evade these mechanisms. ABSTRACT: Lyme disease is the most common vector-borne illness in North America and Europe. Its causative agents are spirochetes of the Borrelia burgdorferi sensu latu complex. Infection with borreliae can manifest in different tissues, most commonly in the skin and joints, but in severe cases also in the nervous systems and the heart. The immune response of the host is a crucial factor for preventing the development or progression of Lyme disease. Macrophages are part of the innate immune system and thus one of the first cells to encounter infecting borreliae. As professional phagocytes, they are capable of recognition, uptake, intracellular processing and final elimination of borreliae. This sequence of events involves the initial capture and internalization by actin-rich cellular protrusions, filopodia and coiling pseudopods. Uptake into phagosomes is followed by compaction of the elongated spirochetes and degradation in mature phagolysosomes. In this review, we discuss the current knowledge about the processes and molecular mechanisms involved in recognition, capturing, uptake and intracellular processing of Borrelia by human macrophages. Moreover, we highlight interactions between macrophages and other cells of the immune system during these processes and point out open questions in the intracellular processing of borreliae, which include potential escape strategies of Borrelia.