Polysaccharide of Asparagus cochinchinensis (Lour.) Merr regulates macrophage immune response and epigenetic memory through TLR4-JNK/p38/ERK signaling pathway and histone modification.

BACKGROUND: Innate immune memory of macrophages is closely linked to histone modifications. While various studies have demonstrated that the polysaccharide of Asparagus cochinchinensis (Lour.) Merr (ACMP), extracted through alcohol-alkali extraction, enhances macrophages' non-specific immune function; no literature currently addresses whether ACMP's regulatory effect is related to innate immune memory and histone modification. PURPOSE: This study aims to investigate if ACMP induces innate immune memory emergence in macrophages via pattern recognition receptor (PRR). STUDY DESIGN: After co-incubating different doses of ACMP with RAW264.7 cells and BMDM cells, we observed changes in signaling pathways related to PRR and assessed the presence of innate immune memory phenomenon in the cells. METHODS: We observed the morphological characteristics of the ACMP using a scanning electron microscope, infrared spectrum, and HPLC pre-column derivatization method. We used q-PCR, Western blot, RNA-seq, and CUT&Tag-seq methods to examine ACMP's regulation of macrophage immune response and innate immune memory and explored its specific mechanism. RESULTS: ACMP, primarily composed of Man, GlcN, Rha, Fuc, GalA, Xyl, Glc, Gal, Ara, and, exhibited a molar ratio of each monosaccharide (1.41: 0.35: 0.49: 0.18: 1.00: 97.12: 0.36: 3.58: 1.14). ACMP regulated immunological function in macrophages through the TLR4-MAPK-JNK/p38/ERK pathway. ACMP induced elevated levels of chromosomal H3K4me1, enhancing TNF-α, IL-1ß, and other genes' responsiveness, allowing macrophages to develop innate immune memory to ACMP stimulation. CONCLUSION: This study first time demonstrates that ACMP regulates immunological function through the TLR4-MAPK-JNK/ERK/p38 signaling pathway, distinct from prior reports. ACMP induces innate immune memory in macrophages in response to its immune stimulation by promoting increased H3K4me1 on chromosomes. This mechanism may be crucial in how plant polysaccharides regulate macrophages and the body's immune function.

RNA-Seq and 16S rRNA Reveals That Tian-Dong-Tang-Gan Powder Alleviates Environmental Stress-Induced Decline in Immune and Antioxidant Function and Gut Microbiota Dysbiosis in Litopenaeus vannami.

Ammonia stress and nitrite stress can induce immune depression and oxidative stress in Litopenaeus vannami (L. vannamei). Earlier reports showed that L. vannamei immunity, resistance to ammonia stress, and resistance to nitrite stress improved after Tian-Dong-Tang-Gan Powder (TDTGP) treatment, but the mechanism is not clear. In this study, three thousand L. vannamei were fed different doses of TDTGP for 35 days and then subjected to ammonia and nitrite stress treatments for 72 h. Transcriptome and 16-Seq ribosomal RNA gene sequencing (16S rRNA-seq) were used to analyze hepatopancreas gene expression and changes in gut microbiota abundance in each group. The results showed that after TDTGP treatment, hepatopancreas mRNA expression levels of immunity- and antioxidant-related genes were increased, the abundance of Vibrionaceae in the gut microbiota was decreased, and the abundance of Rhodobacteraceae and Flavobacteriaceae was increased. In addition, after TDTGP treatment, the effects of ammonia and nitrite stress on the mRNA expression of Pu, cat-4, PPAF2, HO, Hsp90b1, etc. were reduced and the disruption of the gut microbiota was alleviated. In short, TDTGP can regulate the immunity and antioxidant of L. vannamei by increasing the expression levels of immunity- and antioxidant-related genes and regulating the abundance of Rhodobacteraceae and Flavobacteriaceae in the gut microbiota.