Langerhans Cell Deficiency ImpairsIxodes scapularisSuppression of Th1 Responses in Mice

Abstract

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 ConAstimulated 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.

Intradermal Immunization Triggers Epidermal Langerhans Cell Mobilization Required for CD8 T-Cell Immune Responses

“…Indeed, the nature of the vaccine preparation or of the pathogen, as well as the antigen dose and the route of administration, are important parameters that could influence the differential involvement of LCs or CD207 þ DCs for the induction of immune responses. LCs are undeniably of major importance for the induction of Th1 immune responses; i.e., to fight Borrelia burdorferi in the Lyme disease (Vesely et al, 2009), or for the generation of alloreactive cytotoxic T lymphocytes in the skin after bone marrow stem cell transplantation (graft-versus-host disease; Merad et al, 2004).…”

Langerhans Cells Suppress Contact Hypersensitivity Responses Via Cognate CD4 Interaction and Langerhans Cell-Derived IL-10

“…Thus, LC actually function to suppress the CHS response. LC-mediated suppression also inhibits rejection of minor-mismatched skin grafts and limits Th1 responses after tick infestation(15, 16). …”

Modulation of host immunity by tick saliva

“…I. scapularis saliva has displayed various effects on bone marrow-derived DCs: it inhibited TNF and IL-12 production upon stimulation of different TLRs, in particular TLR-2, TLR-4, or TLR-9 [77], and the DC’s ability to stimulate antigen-specific CD4+ proliferation and IL-2 production was also suppressed [77]. LC-deficient mice induced Th1 responses after I. scapularis infestation, demonstrating the requirement for LCs in attenuating tick-mediated Th1 responses in regional lymph nodes [78]. …”