S-Layer From Lactobacillus brevis Modulates Antigen-Presenting Cell Functions via the Mincle-Syk-Card9 Axis

TLDR

C‑type lectin receptors, including the mucosa‑associated Mincle, are key pattern‑recognition receptors that mediate gut microbiota‑driven immune homeostasis. The study aimed to identify Mincle as a receptor for Lactobacillus brevis S‑layer and assess its effect on bone marrow‑derived dendritic cell functions. Using Lactobacillus brevis S‑layer stimulation of bone marrow‑derived dendritic cells, the authors examined cytokine release and T‑cell priming in wild‑type versus Mincle, CARD9, or Syk conditional knockout mice. S‑layer binding to Mincle induced a balanced cytokine profile and normal CD4⁺ T‑cell priming, whereas loss of Mincle, CARD9 or Syk disrupted this balance, increasing TNF/IL‑6 and decreasing IL‑10/TGF‑β and enhancing IFN‑γ production.

Abstract

C-type lectin receptors (CLRs) are pattern recognition receptors that are crucial in the innate immune response. The gastrointestinal tract contributes significantly to the maintenance of immune homeostasis; it is the shelter for billions of microorganisms including many genera of Lactobacillus sp. Previously, it was shown that host-CLR interactions with gut microbiota play a crucial role in this context. The Macrophage-inducible C-type lectin (Mincle) is a Syk-coupled CLR that contributes to sensing of mucosa-associated commensals. In this study, we identified Mincle as a receptor for the Surface (S)-layer of the probiotic bacteria Lactobacillus brevis modulating GM-CSF bone marrow-derived cells (BMDCs) functions. We found that the S-layer/Mincle interaction led to a balanced cytokine response in BMDCs by triggering the release of both pro- and anti-inflammatory cytokines. In contrast, BMDCs derived from Mincle −/− , CARD9 −/− or conditional Syk −/− mice failed to maintain this balance, thus leading to an increased production of the pro-inflammatory cytokines TNF and IL-6, whereas the levels of the anti-inflammatory cytokines IL-10 and TGF-β were markedly decreased. Importantly, this was accompanied by an altered CD4 + T cell priming capacity of Mincle −/− BMDCs resulting in an increased CD4 + T cell IFN-γ production upon stimulation with L. brevis S-layer. Our results contribute to the understanding of how commensal bacteria regulate antigen-presenting cell (APC) functions and highlight the importance of the Mincle/Syk/Card9 axis in APCs as a key factor in host-microbiota interactions.