Treatment of Borrelia burgdorferi-Infected Mice with Apoptotic Cells Attenuates Lyme Arthritis via PPAR-γ
Infection of mice with Borrelia burgdorferi causes an inflammatory arthritis that peaks 3-4 wk post-infection and then spontaneously resolves. Although the recruitment of neutrophils is known to drive the development of arthritis, mechanisms of disease resolution remain unclear.
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Efficient clearance of apoptotic cells (AC) is likely an important component of arthritis resolution. In this article, we show the number of AC increases in the joints of B. burgdorferi-infected mice around day 21 post-infection and peaks around day 28. Injection of AC directly into the ankles of B. burgdorferi-infected mice limited ankle swelling but had no effect on spirochete clearance or arthritis severity scores.
In vitro, addition of AC to bone marrow macrophage cultures decreased B. burgdorferi-induced TNF-α and KC and increased IL-10. In addition, phagocytosis of B. burgdorferi and neutrophil migration to LTB4 were inhibited by AC. Exogenous AC caused an increase in peroxisome proliferator-activated receptor-γ (PPAR-γ) expression both in vitro and in vivo during B. burgdorferi infection. The PPAR-γ agonist rosiglitazone elicited similar changes in macrophage cytokine production and neutrophil migration as exogenous AC.
Addition of the PPAR-γ antagonist GW 9662 abrogated the effects of AC in vitro. Injection of rosiglitazone directly into the tibiotarsal joints of B. burgdorferi-infected mice decreased ankle swelling and immune cell recruitment, similar to the injection of AC.
These results suggest that clearance of AC plays a role in the resolution of inflammation during experimental Lyme arthritis through the activation of PPAR-γ. PPAR-γ agonists, such as rosiglitazone, may therefore be effective treatments for inducing arthritis resolution
Source: By Hilliard KA and CR Brown. Treatment of Borrelia burgdorferi-Infected Mice with Apoptotic Cells Attenuates Lyme Arthritis via PPAR-γ. J Immunol. 2019 Jan 30. pii: ji1801179. doi: 10.4049/jimmunol.1801179. [Epub ahead of print]