Follistatin-like protein 1 is a critical mediator of experimental Lyme arthritis and the humoral response to Borrelia burgdorferi infection.
Follistatin-like protein 1 (FSTL-1) has recently been described as a critical mediator of CIA and a marker of disease activity. Lyme arthritis, caused by Borrelia burgdorferi, shares similarities with autoimmune arthritis and the experimental murine model collagen-induced arthritis (CIA). Because FSTL-1 is important in CIA and autoimmune arthritides, and Lyme arthritis shares similarities with CIA, we hypothesized that FSTL-1 may be an important mediator of Lyme arthritis. We demonstrate for the first time that FSTL-1 is induced by B. burgdorferi infection and is required for the development of Lyme arthritis in a murine model, utilizing a gene insertion to generate FSTL-1 hypomorphic mice. Using qPCR and qRT-PCR, we found that despite similar early infectious burden, FSTL-1 hypomorphic mice have improved spirochetal clearance in the face of attenuated arthritis and inflammatory cytokine production. Further, FSTL-1 mediates pathogen-specific antibody production and antigen recognition when assessed by ELISA and one- and two-dimensional immunoblotting. This study is the first to describe a role for FSTL-1 in the development of Lyme arthritis and anti-Borrelia response, and the first to demonstrate a role for FSTL-1 in response to infection, highlighting the potential for FSTL-1 as a target in the treatment of B. burgdorferi infection.
Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Brian T
BT
Campfield
Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Christi L
CL
Nolder
Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Anthony
A
Marinov
Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Daniel
D
Bushnell
Department of Pathology, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Amy
A
Davis
Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Caressa
C
Spychala
Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA.
Raphael
R
Hirsch
Department of Pediatrics, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Electronic address: nowaaj@chp.edu.
Andrew J
AJ
Nowalk
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D025065:Borrelia burgdorferi / Q000276:immunology / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D038702:Follistatin-Related Proteins / Q000378:metabolism*; D008193:Lyme Disease / Q000276:immunology / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction
D000907:Antibodies, Bacterial; D016207:Cytokines; D038702:Follistatin-Related Proteins
Arthritis; Borrelia burgdorferi; FSTL-1; Lyme disease; Mouse model; humoral immunity