Abstract
Dendritic cells play an essential role in bridging innate and adaptive immunity by recognizing cellular stress including pathogen- and damage-associated molecular patterns and by shaping the types of antigen-specific T cell immunity. Although lidocaine is widely used in clinical settings that trigger cellular stress, it remains unclear whether such treatment impacts the activation of innate immune cells and subsequent differentiation of T cells. Here we showed that lidocaine inhibited the production of IL–6, TNFα and IL–12 from dendritic cells in response to toll-like receptor ligands including lipopolysaccharide, poly(I:C) and R837 in a dose-dependent manner. Notably, the differentiation of Th1 cells was significantly suppressed by the addition of lidocaine while the same treatment had little effect on the differentiation of Th17, Th2 and regulatory T cells in vitro. Moreover, lidocaine suppressed the ovalbumin-specific Th1 cell responses in vivo induced by the adoptive transfer of ovalbumin-pulsed dendritic cells. These results demonstrate that lidocaine inhibits the activation of dendritic cells in response to toll-like receptor signals and subsequently suppresses the differentiation of Th1 cell responses.
Highlights
Recognition of pathogen-associated molecular patterns (PAMPs) such as toll-like receptor (TLR) ligands as well as damage-associated molecular patterns (DAMPs) such as high mobility group box 1 (HMGB1) by innate immune receptors leads to the activation of macrophages and dendritic cells [1, 2]
Cytokines in IL–12 family, IL–6 and IL–1β are produced by dendritic cells upon PAMPs and DAMPs doi:10.1371/journal.pone.0139845.g001
Our results demonstrate that lidocaine dampens the production of pro-inflammatory cytokines from dendritic cells upon TLR stimulation and suppresses the differentiation of Th1 cells in vitro as well as in vivo
Summary
Recognition of pathogen-associated molecular patterns (PAMPs) such as toll-like receptor (TLR) ligands as well as damage-associated molecular patterns (DAMPs) such as high mobility group box 1 (HMGB1) by innate immune receptors leads to the activation of macrophages and dendritic cells [1, 2]. Tissue resident macrophages are known to sense these exogenous and endogenous stimuli to produce immune modulatory molecules such as IL–6, TNFα as well as reactive nitrogen species and reactive oxygen species that can mediate tissue inflammation [3, 4]. Activation of dendritic cells by PAMPs and DAMPs triggers the production of pro- or anti-inflammatory cytokines, and induces their migration into lymph nodes and subsequent activation of T cells in an antigen-specific manner [5, 6].
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