Overview
Innate immunity is the body's first-line, non-specific defense against pathogens — comprising physical barriers (epithelium, mucus), antimicrobial molecules (calprotectin, lactoferrin, defensins), pattern recognition receptors (TLRs, NOD-like receptors), and phagocytic cells (macrophages, neutrophils, dendritic cells). In the WikiBiome framework, innate immunity is inseparable from nutritional immunity — the host strategy of restricting essential metals from pathogens.
Metal-Mediated Innate Defense
The innate immune system deploys metals as weapons:
- calprotectin: Released by neutrophils; sequesters zinc and manganese, starving pathogens of essential cofactors.
- lactoferrin: Binds free iron at mucosal surfaces; denies iron to siderophore-dependent pathogens.
- hepcidin: IL-6-induced master iron regulator; sequesters systemic iron during infection.
- lipocalin 2: Neutralizes bacterial enterobactin (the strongest known siderophore).
- Copper burst: Macrophages pump toxic copper into phagosomes to kill engulfed bacteria.
- Zinc intoxication: Macrophages deliver lethal zinc doses to Salmonella-containing vacuoles.
Microbiome Shaping
The innate immune system shapes the microbiome, and the microbiome shapes innate immunity:
- TLR signaling: Microbial LPS (TLR4), lipoteichoic acid (TLR2), flagellin (TLR5), and CpG DNA (TLR9) train innate immune responses chen 2024 esophageal dysbiosis tlr2 barrier integrity gerd.
- Peptidoglycan recognition proteins (PGRPs): Kill bacteria via metal-mediated oxidative, thiol, and osmotic stress — a direct intersection of innate immunity and metal toxicity kashyap 2014 pgrps kill bacteria metal stress.
- Intestinal immunity: Iron homeostasis in the gut directly modulates innate immune cell function bao 2024 iron homeostasis intestinal immunity gut microbiota.
- Crohn's disease: Defective innate immunity (NOD2 mutations) leads to impaired bacterial clearance and chronic inflammation haag 2015 intestinal microbiota innate immunity crohns.
Cross-References
- nutritional immunity — metal restriction as innate antimicrobial strategy
- calprotectin — neutrophil-derived Zn/Mn sequestration
- lactoferrin — mucosal iron sequestration
- hepcidin — systemic iron regulation
- toll like receptors — pattern recognition driving innate responses
- nf kappa b — downstream signaling from pattern recognition
- inflammation — innate immune activation driving chronic inflammation