Abstract
Lactic acid bacteria (LAB) are one of the major commensal species in the small intestine and known for contributing to maintenance of protective immunity and immune homeostasis. However, currently there has been no evidence regarding the cellular mechanisms involved in the probiotic effects of LAB on human immune cells. Here, we demonstrated that LAB double-stranded RNA (dsRNA) triggered interferon-β (IFN-β) production by human dendritic cells (DCs), which activated IFN-γ-producing T cells. Interleukin-12 (IL-12) secretion from human DCs in response to LAB was abrogated by depletion of bacterial dsRNA, and was attenuated by neutralizing IFN-β, indicating LAB dsRNA primarily activated the IFN-β/IL-12 pathway. Moreover, the induction of IL-12 secretion from DCs by LAB was abolished by the inhibition of endosomal acidification, confirming the critical role of the endosomal digestion of LAB. In a coculture of human naïve CD4+ T cells and BDCA1+ DCs, DCs stimulated with LAB containing dsRNA induced IFN-γ-producing T cells. These results indicate that human DCs activated by LAB enhance Th1 immunity depending on IFN-β secretion in response to bacterial dsRNA.
Highlights
Exposure to bacterial or viral components is critical for the functional maturation of host immunity, including innate and acquired cell populations such as IFN-γ-producing Th1 cells and antiinflammatory regulatory T cells
We previously reported a higher amount of double-stranded RNA (dsRNA) present in Lactic acid bacteria (LAB) compared with pathogenic bacteria, which contributed to anti-inflammation via induction of IFN-β secretion from murine dendritic cells (DCs) [28]
IRF7 and IRF8, but slightly attenuated IL-6, IL-10 production and IRF1 mRNA expression (Figures 2B,C; Figure S2C,D in Supplementary Material). These results indicate that dsRNA is essential for the induction of IFN-β secretion and IRF7/8 mRNA expression in Monocyte-derived DCs (moDCs) in response to K15, and that IL-12 secretion partially depends on this IFN-β response
Summary
Exposure to bacterial or viral components is critical for the functional maturation of host immunity, including innate and acquired cell populations such as IFN-γ-producing Th1 cells and antiinflammatory regulatory T cells. The recognition of a variety of components from microorganisms by innate immune receptors triggers robust immune responses such as cytokine production [10]. Toll-like receptors (TLRs) play a critical role in the recognition of structurally conserved bacterial and viral components, termed pathogen-associated molecular patterns, and signal transduction via TLRs induces rapid. Bacterial dsRNA Activates Human DCs anti-infectious responses and sequentially promotes the development of acquired immunity, resulting in the maintenance of long-term homeostatic protective immunity [11,12,13]. Two subsets of myeloid dendritic cells (DCs), BDCA1+ DCs (mDC1) and BDCA3+ DCs (mDC2), and plasmacytoid DCs (pDCs) are present in peripheral blood mononuclear cells (PBMCs), and mDC1 and pDCs are more abundant compared with mDC2 among these subsets [15,16,17]. mDC1 expressing a variety of TLRs secrete high levels of interleukin-12 (IL-12), while mDC2 expressing high levels of TLR3 secrete IFN-λ, a type III IFN [18]. pDCs express TLR7 and TLR9, and robustly secrete IFN-α in response to viral infection [19,20,21]
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