Lyme Borreliosis and Deficient Mannose-Binding Lectin Pathway of Complement

Abstract

Risk factors for the widely endemic and much-debated tick-borne infection, Lyme borreliosis (LB), are unknown. The mannose-binding lectin (MBL) pathway of the complement cascade has an essential role in the eradication of Borrelia burgdorferi. A sufficient concentration of biologically active MBL in body fluids is an indicator of proper function of the MBL pathway. In this study, we investigated whether impaired MBL pathway function, represented by reduced serum MBL concentration, predisposes individuals to LB. First, we determined a serum MBL concentration cut-off level associated with diminished MBL pathway function in a group of 201 individuals. Then, we identified 350 borrelia Ab+ LB patient serum samples and 350 Ab− control samples from the archives of our laboratory and measured serum MBL concentrations in both sample groups. The concentration data were analyzed statistically using logistic regression, controlling for MBL cut-off, age, gender, and age and gender interaction. Serum MBL concentrations < 787 and < 445 ng/ml were associated with diminished and deficient MBL pathway function, respectively. Using these cut-offs, diminished (41.4 versus 27.4%, p = 0.0027) and deficient (26.3 versus 17.1%, p = 0.0361) MBL pathway functions were observed statistically more frequently in the LB patient samples than in the control samples. Also, the age-adjusted median serum MBL concentrations were significantly lower in the LB patient samples than in the non-LB controls. Our findings indicate that a deficiency in the MBL pathway of the complement cascade is a risk factor for developing disseminated Ab+ LB.

Ixodes scapularis nymph saliva protein blocks host inflammation and complement-mediated killing of Lyme disease agent, Borrelia burgdorferi

“…Since the MBL pathway of complement is important to B. burgdorferi clearance ( Sajanti et al., 2015 ), we next evaluated if r Ixs S41 was protective against killing of serum complement-sensitive B. burgdorferi strain (B314/pBBE22 luc [ luc ]) by complement ( Figure 6C ). Consistent with reduced deposition of the MAC, r Ixs S41 dose-dependently protected the complement-sensitive B. burgdorferi strain from killing by complement.…”

“…Consistent with reduced deposition of the MAC via the Alternative and MBL pathways of complement, r Ixs S41 protected serum complement-sensitive B. burgdorferi strain (B314/pBBE22 luc ) from being killed by complement in a dose-dependent manner. Of note, MBL is known to play an important role in B. burgdorferi clearance ( Sajanti et al., 2015 ; Coumou et al., 2019 ). Based on our data, the mechanism underlying r Ixs S41 protection of B. burgdorferi from complement killing is unknown.…”

Mannose‐binding lectin gene polymorphism in relation to periodontal infection

“…MBL deficiency has been connected to an increased risk for infectious diseases, such as severe respiratory tract infections . Furthermore, a deficient MBL pathway of the complement system seems to be a risk factor for bacterial infections, such as Lyme borreliosis caused by Borrelia burgdorferi and pertussis caused by Bordetella pertussis . In a study by Maffei et al .…”