Macrophage LTB 4 drives efficient phagocytosis of Borrelia burgdorferi via BLT1 or BLT2.

Unresolved experimental Lyme arthritis in C3H 5-lipoxygenase (5-LOX) ^-/- mice is associated with impaired macrophage phagocytosis of Borrelia burgdorferi In the present study, we further investigated the effects of the 5-LOX metabolite, leukotriene (LT)B ₄ on phagocytosis of B. burgdorferi Bone marrow-derived macrophages (BMDMs) from 5-LOX ^-/- mice were defective in the uptake and killing of B. burgdorferi from the earliest stages of spirochete internalization. BMDMs from mice deficient for the LTB ₄ high-affinity receptor (BLT1 ^-/- ) were also unable to efficiently phagocytose B. burgdorferi Addition of exogenous LTB ₄ augmented the phagocytic capability of BMDMs from both 5-LOX ^-/- and BLT1 ^-/- mice, suggesting that the low-affinity LTB ₄ receptor, BLT2, might be involved. Blocking BLT2 activity with the specific antagonist, LY255283, inhibited phagocytosis in LTB ₄ -stimulated BLT1 ^-/- BMDMs, demonstrating a role for BLT2. However, the lack of a phagocytic defect in BLT2 ^-/- BMDMs suggested that this was a compensatory effect. In contrast, 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid, a natural BLT2-specific high-affinity ligand, and resolvin E1, a BLT1 agonist, were both unable to boost phagocytosis in BMDMs from either 5-LOX ^-/- or BLT1 ^-/- mice, suggesting a specific role for LTB ₄ in mediating phagocytosis in murine macrophages. This study demonstrates that LTB ₄ promotes macrophage phagocytosis of bacteria via BLT1, and that BLT2 can fulfill this role in the absence of BLT1.
(Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)