Role of IL-17, transforming growth factor-β, and IL-6 in the development of arthritis and production of anti-outer surface protein A borreliacidal antibodies in Borrelia-vaccinated and -challenged mice

• Published in: FEMS immunology and medical microbiology Vol. 53; no. 2; pp. 265 - 274
• Main Authors: Nardelli, Dean T, Kevin Luk, Kee Hang, Kotloski, Nicholas J, Warner, Thomas F, Torrealba, Jose R, Callister, Steven M, Schell, Ronald F
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.07.2008; Blackwell Publishing Ltd; Blackwell; Oxford University Press
• Subjects: Animals; Ankle; Antibodies; Antibodies, Bacterial - blood; Antigens, Surface - immunology; Applied microbiology; Arthritis; Arthritis - immunology; Arthritis - pathology; Bacterial diseases; Bacterial Outer Membrane Proteins - immunology; Bacterial Vaccines - immunology; Bacteriology; Biological and medical sciences; Borrelia; Borrelia burgdorferi; Borrelia burgdorferi - immunology; Borrelia infections; Cytokines; Edema; Fundamental and applied biological sciences. Psychology; Growth factors; Human bacterial diseases; IL-17; Immunoglobulins; Infectious diseases; Interleukin 17; Interleukin 6; Interleukin-17 - immunology; Interleukin-6 - immunology; Joint diseases; Lipoproteins - immunology; Lyme arthritis; Lyme Disease - immunology; Lyme Disease - pathology; Medical sciences; Mice; Microbiology; Miscellaneous; Outer surface protein A; Protein A; Proteins; Surface protein A; Transforming Growth Factor beta - immunology; Transforming growth factor-b; Tropical bacterial diseases; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); arthritis; IL-17; Lyme arthritis; Lyme disease; Spirochaetaceae; Microbiology; Transforming growth factor β; Diseases of the osteoarticular system; Arthritis; Interleukin 6; Immunology; Spirochaetosis; Bacteria; Borrelia burgdorferi; Spirochaetales; Antibody; Borrelia infection; Cytokine; Rodentia; Vaccine; Protein; Infection; Vertebrata; Mammalia; Borrelia; Mouse; Bacteriosis
• ISSN: 0928-8244; 1574-695X; 2049-632X
• DOI: 10.1111/j.1574-695X.2008.00431.x

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)-β, are also involved in the development of arthritis. Vaccinated and challenged mice administered either anti-TGF-β 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-β in the adaptive immune events leading to the development of Borrelia-induced arthritis.