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Stimulation of Pattern Recognition Receptors (PRRs) via Microbial Associated Molecular Patterns (MAMPs)
Microbial Associated Molecular Patterns (MAMPs) are a recently described category of Pattern Recognition Receptors (PRRs) ligands that includes molecular patterns found in both pathogenic and commensal microbes
Microbial components that are intrinsic, such as lipopolysaccharide (LPS) and muramyl dipeptide (MDP), function as microbe-associated molecular patterns (MAMPs). These components engage with the host's pattern recognition receptors (PRRs), including Toll-like receptor (TLR) and nucleotide-binding oligomerization domain (NOD). This interaction triggers the host's innate immune response.
After the interaction of MAMPs with their PRRs, antimicrobial peptides (AMPs) from Paneth cells and Oxidative Stress / Reactive Oxygen Species (ROS), cytokines from enterocytes, restrict the growth of pathogens.
Bacterial Microbial Associated Molecular Patterns (MAMPs) can stimulate pattern recognition receptors (PRRs) (including extracellular Toll-Like Receptors (TLRs) and Formylated peptide receptors (FPRs) or intracellular NOD-like receptors (NLRs). The intensity, duration, and spatial origin of the subsequent signaling reactions determine the strength of the MAMP effect: weak (cytoprotection), moderate (inflammatory response), and strong (apoptosis).
NLRC2 / NOD2 (NOD-like receptor family CARD Domain-Containing Protein 2) is an intracellular Pattern Recognition Receptors (PRRs). In the ctosol, it detects muramyl dipeptide (MDP) as a part of peptidoglycan in both Gram-positive and Gram-negative bacteria. The leucine-rich repeat (LRR) domain makes its sensing and triggers the cytokine production. Chemokines and antimicrobial peptides (AMPs) are also produced through NFKB signaling.
NOD2 regulates Intestinal homeostasis through maintaining functions of crucial Enterocytes / Intestinal Epithelial Cells (IECs). In goblet cells (GCs), NOD2 regulates mucus secretion. It affects mucin granules and GC numbers and also influences cell morphology.
In Paneth cells, NOD2 helps in lysozyme sorting. It aids in producing certain Antimicrobial peptides (AMPs): Regenerating islet-derived protein 3 gamma (REG3G), Alfa-defensins, REG3B (mouse). It may also maintain Paneth cell morphology.
NOD2 is strongly expressed in Lgr5+ crypt-base columnar (CBC) cells. It regulates cell survival and aids in stem cell self-renewal. NOD2 is crucial for intraepithelial lymphocytes maintaining their proliferation and also supporting their Interleukin-15 (IL-15) production.