Interleukin-23 is required for development of arthritis in mice vaccinated and challenged with Borrelia species.
We recently hypothesized that T helper 17 (Th17) cells and their associated cytokines are involved in the development of arthritis following infection with Borrelia burgdorferi. Here, we show that interleukin-23 (IL-23), a survival factor for Th17 cells, is required for the induction of arthritis in mice vaccinated with B. burgdorferi strain 297 and challenged with "Borrelia bissettii." When Borrelia-vaccinated and -challenged mice were given antibodies to the p19 subunit of IL-23, they failed to develop the histopathological changes observed in untreated vaccinated and challenged mice. In addition, viable B. bissettii organisms stimulated the secretion of IL-17 from Borrelia-immune lymph node cells during in vitro culture. When anti-IL-23 p19 antibody was included in cultures of B. bissettii organisms and Borrelia-immune lymph node cells, the production of IL-17 was reduced to levels observed in cultures containing immune cells alone. Taken together, these results support the hypothesis that Th17 cell-associated cytokines are involved in the development of Borrelia-mediated arthritis. These findings provide insight into previously overlooked immune mechanisms responsible for the development of Lyme arthritis.
Kotloski
Nicholas J
NJ
University of Wisconsin, Wisconsin State Laboratory of Hygiene, 465 Henry Mall, Madison, WI 53706, USA.
Nardelli
Dean T
DT
Peterson
Sara Heil
SH
Torrealba
Jose R
JR
Warner
Thomas F
TF
Callister
Steven M
SM
Schell
Ronald F
RF
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use; D001898:Borrelia / Q000145:classification / Q000276:immunology / Q000472:pathogenicity*; D025065:Borrelia burgdorferi / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism*; D008193:Lyme Disease / Q000276:immunology* / Q000503:physiopathology* / Q000517:prevention & control; D022123:Lyme Disease Vaccines / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination
D000906:Antibodies; D053759:Interleukin-23; D022123:Lyme Disease Vaccines