Local Production of Interferon Gamma by Invariant Natural Killer T cells Modulates Acute Lyme Carditis

• Published in: The Journal of immunology (1950) Vol. 182; no. 6; pp. 3728 - 3734
• Main Authors: Olson, Chris M., Bates, Tonya C., Izadi, Hooman, Radolf, Justin D., Huber, Sally A., Boyson, Jonathan E., Anguita, Juan
• Format: Journal Article
• Language: English
• Published: 15-03-2009
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0804111

The Lyme disease spirochete,
Borrelia burgdorferi
, is the only known human pathogen that directly activates invariant natural killer T (iNKT) cells. The number and activation kinetics of iNKT cells vary greatly among different strains of mice. We now report the role of the iNKT cell response in the pathogenesis of Lyme disease using C57Bl/6 mice, a strain with optimal iNKT cell activation that is resistant to the development of spirochetal-induced inflammation. During experimental infection of B6 mice with
B. burgdorferi
, iNKT cells localize to the inflamed heart where they are activated by CD1d-expressing macrophages. Activation of iNKT cells in vivo results in the production of IFNγ, which we demonstrate ameliorates the severity of murine Lyme carditis by at least two mechanisms. First, IFNγ enhances the recognition of
B. burgdorferi
by macrophages, leading to increased phagocytosis of the spirochete. Secondly, IFNγ activation of macrophages increases the surface expression of CD1d, thereby facilitating further iNKT activation. Collectively, our data demonstrate that in the resistant background, B6, iNKT cells modulate the severity of murine Lyme carditis through the action of IFNγ, which appears to self-renew through a positive feedback loop during infection.