New Aspects Towards a Molecular Understanding of the Allicin Immunostimulatory Mechanism via Colec12, MARCO, and SCARB1 Receptors

The allicin pleiotropic effects, which include anti-inflammatory, anti-oxidant, anti-tumoral, and antibacterial actions, were well demonstrated and correlated with various molecular pathways. The immunostimulatory mechanism of allicin has not been elucidated; however, there is a possible cytokine stimulation from immunoglobulin release caused by allicin. In this study, when Wistar female rats and CD19+ lymphocytes were treated with three different doses of allicin, immunoglobulins, glutathione, and oxidative stress markers were assayed. Molecular docking was performed between S-allylmercaptoglutathione (GSSA)—a circulating form of allicin in in vivo systems formed by the allicin interaction with glutathione (GSH)—and scavenger receptors class A and B from macrophages, as well as CD19+ B lymphocytes. Our data demonstrated a humoral immunostimulatory effect of allicin in rats and direct stimulation of B lymphocytes by S-allyl-mercapto-glutathione, both correlated with decreased catalase (CAT) activity. The molecular docking revealed that S-allyl-mercapto-glutathione interacting with Colec12, MARCO (class A), and SCARB1 (class B) scavenger receptors in in vitro tests demonstrates a direct stimulation of immunoglobulin secretion by GSSA in CD19+ B lymphocytes. These data collectively indicate that GSSA stimulates immunoglobulin secretion by binding on scavenger receptors class B type 1 (SCARB1) from CD19+ B lymphocytes.

Lymphocyte-Specific Protein Tyrosine Kinase (LCK) is Involved in the Aryl Hydrocarbon Receptor-Mediated Impairment of Immunoglobulin Secretion in Human Primary B Cells

The aryl hydrocarbon receptor (AHR) is a cytosolic ligand-activated transcription factor involved in xenobiotic sensing, cell cycle regulation, and cell development. In humans, the activation of AHR by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a high affinity AHR-ligand, impairs the secretion of immunoglobulin M (IgM) to suppress humoral immunity. However, the mechanisms bridging the activation of AHR and the impairment of IgM secretion by human primary B cells remain poorly understood. Recent transcriptomic analysis revealed upregulation of lymphocyte-specific protein tyrosine kinase (LCK) in AHR-activated human primary B cells. LCK is a well-characterized tyrosine kinase that phosphorylates critical signaling proteins involved in activation and cytokine production in T cells. Conversely, the role of LCK in human primary B cells is not well understood. In the current studies, we have verified the transcriptomic finding by detecting AHR-mediated upregulation of LCK protein in human primary B cells. We also confirmed the role of AHR in the upregulation of LCK by using a specific AHR antagonist, which abolished the AHR-mediated increase of LCK. Furthermore, we have confirmed the role of LCK in the AHR-mediated suppression of IgM by using LCK specific inhibitors, which restored the IgM secretion by human B cells in the presence of TCDD. Collectively, the current studies demonstrate a novel role of LCK in IgM response and provide new insights into the mechanism for AHR-mediated impairment of immunoglobulin secretion by human primary B cells.