Antimicrobial Peptide-Mediated Immune Activation

The innate immune response is the body's first line of defense against infection. Certain intrinsic components of microorganisms such as lipopolysaccharides (interacting with host recognition receptors [e.g., toll-like receptors (TLRs)] activate multiple intracellular signaling networks to generate a variety of effector molecules, including antimicrobial peptides , participate in the host immune response. A large number of research results show that antimicrobial peptides can induce the production of chemokines and enhance their activity. Secreted antimicrobial peptides (such as LL.37, HNP-1, HNP.2, hBD-1 and hBD.2) It can recruit neutrophils, monocytes, eosinophils, dendritic cells (DC) and T lymphocytes to migrate to the site of infection through direct or indirect action, enhancing the classic pro-inflammatory response in innate immunity, exert an anti-infective effect

Antimicrobial peptides can activate the body's innate immune defense through a variety of ways, so how does he activate this process? A large number of studies have confirmed that antimicrobial peptides may affect the upstream key signaling pathways in the innate immune process, and then promote its downstream corresponding genes expression. For example: LL. 37 and D. Defensins can activate mitogen-activated protein kinases (MAPKs, such as p38 and p44/42) in monocytes, mast cells and keratinocytes. LL. 37 can also regulate the expression of epidermal growth factor receptor (EGFR) in keratinocytes by activating signal transducer and activator of transcription 3 (STAT3)'261. cathelicidins and defensins can also activate NF-KB, P13K, activator protein-1 (activator protein-1, AP-1) and Janus kinase (JAK) signaling pathways, and then activate its downstream signals. At the same time, MAPKs-mediated signaling pathways such as NF-KB can activate the production of pro-inflammatory factors and reactive oxygen species, and coordinate the stimulation of innate immune responses such as various types of immune cells. LL-37 can also activate p38 MAPK signaling in monocytes through direct interaction with GAPDH, thereby affecting host defense function