Macrophage LTB₄ drives efficient phagocytosis of Borrelia burgdorferi via BLT1 or BLT2.

ABSTRACT: 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)B₄ 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 LTB₄ high-affinity receptor (BLT1^-/-) were also unable to efficiently phagocytose B. burgdorferi Addition of exogenous LTB₄ augmented the phagocytic capability of BMDMs from both 5-LOX^-/- and BLT1^-/- mice, suggesting that the low-affinity LTB₄ receptor, BLT2, might be involved. Blocking BLT2 activity with the specific antagonist, LY255283, inhibited phagocytosis in LTB₄-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 LTB₄ in mediating phagocytosis in murine macrophages. This study demonstrates that LTB₄ promotes macrophage phagocytosis of bacteria via BLT1, and that BLT2 can fulfill this role in the absence of BLT1.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC5335579 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature