Identification of TLR2/TLR6 signalling lactic acid bacteria for supporting immune regulation

Abstract

Although many lactic acid bacteria (LAB) influence the consumer’s immune status it is not completely understood how this is established. Bacteria-host interactions between bacterial cell-wall components and toll-like receptors (TLRs) have been suggested to play an essential role. Here we investigated the interaction between LABs with reported health effects and TLRs. By using cell-lines expressing single or combination of TLRs, we show that LABs can signal via TLR-dependent and independent pathways. The strains only stimulated and did not inhibit TLRs. We found that several strains such as L. plantarum CCFM634, L. plantarum CCFM734, L. fermentum CCFM381, L. acidophilus CCFM137, and S. thermophilus CCFM218 stimulated TLR2/TLR6. TLR2/TLR6 is essential in immune regulatory processes and of interest for prevention of diseases. Specificity of the TLR2/TLR6 stimulation was confirmed with blocking antibodies. Immunomodulatory properties of LABs were also studied by assessing IL-10 and IL-6 secretion patterns in bacteria-stimulated THP1-derived macrophages, which confirmed species and strain specific effects of the LABs. With this study we provide novel insight in LAB specific host-microbe interactions. Our data demonstrates that interactions between pattern recognition receptors such as TLRs is species and strain specific and underpins the importance of selecting specific strains for promoting specific health effects.

Toll‐like receptor 2 stimulation augments esophageal barrier integrity

“…TJ complex molecules claudin‐1 and ZO‐1 are upregulated within 24 hours following TLR2 stimulation (Figure ). Our results are consistent with findings from other epithelial types, including intestinal, airway, and skin keratinocytes, where TLR2 agonism has been associated with increased expression of TJ complex molecules claudin‐1 and ZO‐1 …”

Lactic Acid Bacteria May Impact Intestinal Barrier Function by Modulating Goblet Cells

“…Toll‐like receptor (TLR) 2 signaling has been proposed to play a vital role in maintaining mucosal homeostasis . Therefore, to determine the time‐dependent kinetics of goblet cell modulation, three out of the 15 LAB strains from different species ( L. plantarum , L. fermentum , and Streptococcus (S.) thermophilus ) which were shown to activate TLR‐signaling pathway and possibly modulate barrier function were first selected to treat LS174T cells. MUC2, TFF3, RETNLB, CHST5, and GAL3ST2 expression was then studied after LAB stimulation for 0.5, 3, 6, 12, 24, and 48 h. Overall, as shown in Figure , different LAB strains possessed differential modulatory potentials on transcription of goblet cell‐related genes, and their effects are time‐dependent.…”

“…All bacterial strains used in this study ( Table ) were provided by Culture Collections of Food Microbiology (CCFM), and aerobically cultured in De Man‐Rogosa‐Sharpe broth (Merck, Darmstadt, Germany) at 37 °C until reaching stationary phase. Bacterial suspension stocks used for experiments were prepared as previously described …”

New Progress Regarding the Use of Lactic Acid Bacteria as Live Delivery Vectors, Treatment of Diseases and Induction of Immune Responses in Different Host Species Focusing on Lactobacillus Species

“…Lactobacillus strains may protect the host from pathogen invasion by increasing the intestinal epithelial barrier. Some LAB microbe-associated molecular patterns (MAMPs) are able of working together with the Toll-like receptor-2 (TLR2), TLR6 and nod-like receptors [94]. Moreover Lactobacillus salivarius JTB07 and Lactobacillus reuteri JTB07 have been reported to upregulate the expression of IL-12, IL-8, IL-6, and IL-1, while Lactobacillus acidophilus JTB05 to upregulate the interferon-gamma expression level of their host cells [45,158,164].…”

“…This demonstrates that probiotic strains of Lactobacillus exert early immunostimulatory effects that may be directly linked to the initial inflammation of the response of human macrophages [98,153]. Lactobacillus species such as Lactobacillus plantarum, and Lactobacillu scasei have been shown to increase the expression of proteins involved in tight junction barrier function which induces several protective mechanisms that restore tissue damage, such as modulation of the stability of tight junctions of the gastrointestinal lining because when become compromised and permeability increases, it allows toxins and other forms of waste to leak into the bloodstream then endotoxins trigger immune activation through Toll-like receptor 4 (TLR4) [94,154].…”