Neutrophil Extracellular Traps Entrap and KillBorrelia burgdorferiSensu Stricto Spirochetes and Are Not Affected byIxodes ricinusTick Saliva

Abstract

Lyme disease is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. They are transmitted mainly by Ixodes ricinus ticks. After a few hours of infestation, neutrophils massively infiltrate the bite site. They can kill Borrelia via phagocytosis, oxidative burst, and hydrolytic enzymes. However, factors in tick saliva promote propagation of the bacteria in the host even in the presence of a large number of neutrophils. The neutrophil extracellular trap (NET) consists in the extrusion of the neutrophil’s own DNA, forming traps that can retain and kill bacteria. The production of reactive oxygen species is apparently associated with the onset of NETs (NETosis). In this article, we describe NET formation at the tick bite site in vivo in mice. We show that Borrelia burgdorferi sensu stricto spirochetes become trapped and killed by NETs in humans and that the bacteria do not seem to release significant nucleases to evade this process. Saliva from I. ricinus did not affect NET formation by human neutrophils or its stability. However, it greatly decreased neutrophil reactive oxygen species production, suggesting that a strong decrease of hydrogen peroxide does not affect NET formation. Finally, round bodies trapped in NETs were observed, some of them staining as live bacteria. This observation could help contribute to a better understanding of the early steps of Borrelia invasion and erythema migrans formation after tick bite.

Tick bites and red meat allergy

“…However, the staining technique they used would probably not identify basophils. On the other hand, a recent study [19] of immune responses to Ixodes scapularis saliva emphasized the role of neutrophils in preventing Borrelia infection.…”

The Nucleotide Excision Repair System of Borrelia burgdorferi Is the Sole Pathway Involved in Repair of DNA Damage by UV Light

“…burgdorferi has been shown to induce the release of NO from macrophages (25) and recruitment of macrophages and neutrophils to organs where it disseminates (22,24,83). However, previous studies showed that inhibition of iNOS using N G -L-monomethyl arginine (LMMA) does not significantly affect the bacterial burden in the heart and joint of C3H/HeJ or BALB/c mice infected with B. burgdorferi (84) and has only a minor effect on survival of the bacterium in the presence of macrophages (25).…”

“…During murine infection, B. burgdorferi disseminates hematogenously to multiple organs, including joint, heart, skin, and bladder (18). Previous studies suggested that during its infectious cycle, B. burgdorferi could be exposed to DNA-damaging conditions and agents (19)(20)(21)(22)(23)(24)(25)(26)(27). However, little is known about the pathways used by B. burgdorferi to repair damaged DNA and if these systems are required for infection in mice.…”

Interactions between host immune response and antigenic variation that control Borrelia burgdorferi population dynamics

“…Here, the recruitment rate of predator-like immune effector cells is a function of the abundance of prey-like B. burgdorferi, resulting in rapid recruitment of immune effector cells and removal of B. burgdorferi when B. burgdorferi population sizes are large, followed by fewer immune effector cells and reduced killing when B. burgdorferi is rare [33]. The recruitment and depletion of immune effector cells such as neutrophils, macrophages and eosinophils have been empirically shown to impact on B. burgdorferi infections within hosts [36][37][38]. Model 3 also predicts continuous fluctuations in B. burgdorferi populations throughout the early stages of infection (Fig.…”