NKT cells prevent chronic joint inflammation after infection with Borrelia burgdorferi.
Borrelia burgdorferi is the etiologic agent of Lyme disease, a multisystem inflammatory disorder that principally targets the skin, joints, heart, and nervous system. The role of T lymphocytes in the development of chronic inflammation resulting from B. burgdorferi infection has been controversial. We previously showed that natural killer T (NKT) cells with an invariant (i) TCR alpha chain (iNKT cells) recognize glycolipids from B. burgdorferi, but did not establish an in vivo role for iNKT cells in Lyme disease pathogenesis. Here, we evaluate the importance of iNKT cells for host defense against these pathogenic spirochetes by using Valpha14i NKT cell-deficient (Jalpha18(-/-)) BALB/c mice. On tick inoculation with B. burgdorferi, Jalpha18(-/-) mice exhibited more severe and prolonged arthritis as well as a reduced ability to clear spirochetes from infected tissues. Valpha14i NKT cell deficiency also resulted in increased production of antibodies directed against both B. burgdorferi protein antigens and borrelial diacylglycerols; the latter finding demonstrates that anti-glycolipid antibody production does not require cognate help from Valpha14i NKT cells. Valpha14i NKT cells in infected wild-type mice expressed surface activation markers and produced IFNgamma in vivo after infection, suggesting a participatory role for this unique population in cellular immunity. Our data are consistent with the hypothesis that the antigen-specific activation of Valpha14i NKT cells is important for the prevention of persistent joint inflammation and spirochete clearance, and they counter the long-standing notion that humoral rather than cellular immunity is sufficient to facilitate Lyme disease resolution.
Tupin
Emmanuel
E
Divisions of Developmental Immunology and Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle Drive, La Jolla, CA 92037, USA.
Benhnia
Mohammed Rafii-El-Idrissi
MR
Kinjo
Yuki
Y
Patsey
Rebeca
R
Lena
Christopher J
CJ
Haller
Matthew C
MC
Caimano
Melissa J
MJ
Imamura
Masakazu
M
Wong
Chi-Huey
CH
Crotty
Shane
S
Radolf
Justin D
JD
Sellati
Timothy J
TJ
Kronenberg
Mitchell
M
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001170:Arthritis, Infectious / Q000276:immunology* / Q000382:microbiology; D025065:Borrelia burgdorferi / Q000276:immunology*; D002908:Chronic Disease; D007371:Interferon-gamma / Q000276:immunology; D007596:Joints / Q000276:immunology* / Q000382:microbiology; D008193:Lyme Disease / Q000150:complications*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000382:microbiology
D000907:Antibodies, Bacterial; D007371:Interferon-gamma