Role of IL-17, transforming growth factor-beta, and IL-6 in the development of arthritis and production of anti-outer surface protein A borreliacidal antibodies in Borrelia-vaccinated and -challenged mice.
We showed recently that the adaptive immune events leading to the development of arthritis in Borrelia burgdorferi isolate 297-vaccinated and Borrelia bissettii-challenged mice involve IL-17. Here, we show in Borrelia-vaccinated and -challenged mice that two cytokines known to induce the production of IL-17, IL-6 and transforming growth factor (TGF)-beta, are also involved in the development of arthritis. Vaccinated and challenged mice administered either anti-TGF-beta or anti-IL-6 antibodies developed histopathologic changes of the hind paws similar to or greater than untreated control mice. By contrast, simultaneous blockage of these cytokines reduced the severity of arthritis in Borrelia-vaccinated and -challenged mice. Moreover, administration of anti-IL-17 antibodies to these dual-antibody-treated mice completely prevented the development of histopathologic changes of the ankle joints, significantly reduced edema of the hind paws, and prevented the production of anti-outer surface protein A borreliacidal antibodies. These findings demonstrate a role for the combined effects of IL-17, IL-6, and TGF-beta in the adaptive immune events leading to the development of Borrelia-induced arthritis.
Nardelli
Dean T
DT
Wisconsin State Laboratory of Hygiene, University of Wisconsin, Madison, WI 53706, USA.
Kevin Luk
Kee Hang
KH
Kotloski
Nicholas J
NJ
Warner
Thomas F
TF
Torrealba
Jose R
JR
Callister
Steven M
SM
Schell
Ronald F
RF
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000954:Antigens, Surface / Q000276:immunology*; D001168:Arthritis / Q000276:immunology* / Q000473:pathology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008074:Lipoproteins / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology / Q000473:pathology; D051379:Mice; D016212:Transforming Growth Factor beta / Q000276:immunology*
D000907:Antibodies, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D020381:Interleukin-17; D015850:Interleukin-6; D008074:Lipoproteins; C072045:OspA protein; D016212:Transforming Growth Factor beta