Langerhans cell deficiency impairs Ixodes scapularis suppression of Th1 responses in mice.
Ixodes scapularis ticks transmit a number of human pathogens, including the Lyme disease spirochete Borrelia burgdorferi. I. scapularis suppresses host immunity in the skin to promote feeding and systemically skew T-helper (Th)-cell differentiation toward Th2 cells in secondary lymphoid organs. Although components of tick saliva are known to influence Th-cell polarization, the mechanism whereby tick feeding in the skin modulates regional and systemic Th-cell responses is unknown. In this study, the role of the epidermal Langerhans cell (LC) subset of skin dendritic cells in tick-mediated Th1/Th2-cell immunomodulation was assessed. Mice deficient in LCs (Langerin-DTA mice) exhibited enhanced lymph node (LN) concanavalin A (ConA)-induced Th1 responses after tick infestation in comparison to results for uninfested Langerin-DTA or wild-type (WT) mice, whereas effects on Th2-cell production of interleukin 4 were more variable. Nonetheless, the altered T-cell response did not impact tick feeding or refeeding. Gamma interferon production by ConA-stimulated LN cells of both WT and LC-deficient mice was enhanced by as much as fourfold after B. burgdorferi-infected-tick feeding, indicating that immunomodulatory effects of tick saliva were not able to attenuate the Th1 immune responses induced by this pathogen. Taken together, these findings show a requirement for LCs in the tick-mediated attenuation of Th1 responses in regional lymph nodes but not in the spleens of mice and show that the presence of a pathogen can overcome the Th1-inhibitory effects of tick feeding on the host.
Vesely
Diana L
DL
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, TAC S-520, 300 Cedar Street, New Haven, CT 06520, USA.
Fish
Durland
D
Shlomchik
Mark J
MJ
Kaplan
Daniel H
DH
Bockenstedt
Linda K
LK
D000818:Animals; D005247:Feeding Behavior; D007108:Immune Tolerance; D018884:Ixodes / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D012463:Saliva / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology