Infection of Interleukin 17 Receptor A-Deficient C3H Mice with Borrelia burgdorferi Does Not Affect Their Development of Lyme Arthritis and Carditis

Abstract

Recently, a number of studies have reported the presence of interleukin 17 (IL-17) in patients with Lyme disease, and several murine studies have suggested a role for this cytokine in the development of Lyme arthritis. However, the role of IL-17 has not been studied using the experimental Lyme borreliosis model of infection of C3H mice with Borrelia burgdorferi. In the current study, we investigated the role of IL-17 in the development of experimental Lyme borreliosis by infecting C3H mice devoid of the common IL-17 receptor A subunit (IL-17RA) and thus deficient in most IL-17 signaling. Infection of both C3H and C3H IL-17RA ؊/؊ mice led to the production of high levels of IL-17 in the serum, low levels in the heart tissue, and no detectable IL-17 in the joint tissue. The development and severity of arthritis and carditis in the C3H IL-17RA ؊/؊ mice were similar to what was seen in wildtype C3H mice. In addition, development of antiborrelia antibodies and clearance of spirochetes from tissues were similar for the two mouse strains. These results demonstrate a limited role for IL-17 signaling through IL-17RA in the development of disease following infection of C3H mice with B. burgdorferi.

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

“…A minimum of 300 cells were counted in random fields from at least two independent coverslips. In some experiments, phagocytosis was measured by flow cytometry, as described (36), using F4/80-labeled BMDMs with similar results. The phagocytic index was calculated by determining the percentage of BMDMs containing at least one spirochete per 300 cells and dividing this number by the value for WT cells × 100.…”

CXCR2 MediatesBrucella-Induced Arthritis in Interferon γ–Deficient Mice

“…Joint slurry was put into sterile dishes, stripped of surrounding tissue, strained through an 80-µM mesh, and washed with complete medium (Roswell Park Memorial Institute [RPMI] 1640 medium, 0.1 mM HEPES, 1 mM sodium pyruvate, 1 mM nonessential amino acids, and 10% FBS). Cells were resuspended in RPMI 1640 medium with 0.1 mM HEPES, and red blood cells were lysed with lysis buffer (final concentration, 0.15 M NH 4 Cl, 10 mM KHCO 3 , and 0.1 mM ethylenediaminetetraacetic acid) [27]. Cells were then washed and stained in fluorescence-activated cell-sorting (FACS) buffer (PBS and 2% FBS).…”

The Lyme Disease Pathogen Borrelia burgdorferi Infects Murine Bone and Induces Trabecular Bone Loss

“…Our data suggest that bone loss at 4 weeks postinfection was not primarily due to increased osteoclastogenesis or osteoclast activation, although it is possible that osteoclast-driven bone loss occurred earlier in infection. This is plausible, because tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, and IL-17, which are systemically upregulated in response to B. burgdorferi infection ( 35 – 38 ), are some of the major inflammatory cytokines that stimulate osteoclastogenesis and osteoclast activation ( 8 , 39 ). TNF-α, IL-1, and IL-6 also suppress differentiation of osteoblasts ( 8 ), which is consistent with our observation that osteoblast numbers were reduced in bones which exhibited osteopenia.…”