Wall teichoic acid-dependent phagocytosis of intact cell walls of Lactiplantibacillus plantarum elicits IL-12 secretion from macrophages

Abstract

Selected lactic acid bacteria can stimulate macrophages and dendritic cells to secrete IL-12, which plays a key role in activating innate and cellular immunity. In this study, we investigated the roles of cell wall teichoic acids (WTAs) displayed on whole intact cell walls (ICWs) of Lactiplantibacillus plantarum in activation of mouse macrophages. ICWs were prepared from whole bacterial cells of several lactobacilli without physical disruption, and thus retaining the overall shapes of the bacteria. WTA-displaying ICWs of several L. plantarum strains, but not WTA-lacking ICWs of strains of other lactobacilli, elicited IL-12 secretion from mouse bone marrow-derived macrophages (BMMs) and mouse macrophage-like J774.1 cells. The ability of the ICWs of L. plantarum to induce IL-12 secretion was abolished by selective chemical elimination of WTAs from ICWs, but was preserved by selective removal of cell wall glycopolymers other than WTAs. BMMs prepared from TLR2- or TLR4-deficient mouse could secret IL-12 upon stimulation with ICWs of L. plantarum and a MyD88 dimerization inhibitor did not affect ICW-mediated IL-12 secretion. WTA-displaying ICWs, but not WTA-lacking ICWs, were ingested in the cells within 30 min. Treatment with inhibitors of actin polymerization abolished IL-12 secretion in response to ICW stimulation and diminished ingestion of ICWs. When overall shapes of ICWs of L. plantarum were physically disrupted, the disrupted ICWs (DCWs) failed to induce IL-12 secretion. However, DCWs and soluble WTAs inhibited ICW-mediated IL-12 secretion from macrophages. Taken together, these results show that WTA-displaying ICWs of L. plantarum can elicit IL-12 production from macrophages via actin-dependent phagocytosis but TLR2 signaling axis independent pathway. WTAs displayed on ICWs are key molecules in the elicitation of IL-12 secretion, and the sizes and shapes of the ICWs have an impact on actin remodeling and subsequent IL-12 production.

Lactiplantibacillus plantarum LOC1 Isolated from Fresh Tea Leaves Modulates Macrophage Response to TLR4 Activation

“…Studies found that lactobacilli with the ability to reduce the severity of intestinal infections can improve the phagocytic activity of macrophages and their capacity to produce inflammatory factors such as TNF-α and IFN-γ [ 45 , 46 ]. It was also reported that immunostimulatory L. plantarum strains activate mouse macrophages enhancing IL-12 production and phagocytosis [ 47 ]. Furthermore, studies demonstrated that among the cytokines induced by immunomodulatory lactobacilli, the most remarkable effect was the increase in TNF-α, IFN-γ, IL-1β, IL-6, and IL-12 for most of the probiotic strains assayed [ 45 , 46 , 48 ].…”

Immunogenic molecules associated with gut bacterial cell walls: chemical structures, immune-modulating functions, and mechanisms

“…The WAT derived from the intact cell wall of the gut probiotic L . plantarum stimulates IL-12 secretion from macrophages ( Kojima et al, 2022 ). The LTA (10) from probiotics have shown beneficial effects on regulation of immune responses.…”

Paraprobiotic derived from Bacillus velezensis GV1 improves immune response and gut microbiota composition in cyclophosphamide-treated immunosuppressed mice

“…Furthermore, recent studies indicate that paraprobiotics manufactured based on this premise exert an influence on immune responses in macrophages and splenocytes ( 16 , 17 ). Additionally, these investigations propose that peptidoglycan, lipoteichoic acid, and wall teichoic acid obtained from gram-positive microorganisms play a role in immune regulation ( 18 – 20 ). Consequently, these findings underscore the immunomodulatory efficacy of compositions derived from gram-positive paraprobiotics.…”