Regulation of AMP secretion by TLRs and NLRs during homeostasis and infection. AMPs, mainly secreted by enterocytes and Paneth cells, are found in the inner mucus layer and play important roles in the barrier against enteric pathogens. At the steady state, microbial-associated molecular patterns, (MAMPs, green stars) from commensal bacteria are sensed by pattern recognition receptors (PRRs). They trigger basal AMP and interleukin-18 (IL-18) production through the activation of NF-κB and inflammasome pathways, respectively. This participates in the tuning of host responses toward tolerance and help maintaining intestinal homeostasis. Loss of homeostasis occurs when pathogens breach the mucus layer, enter in contact with IECs and disrupt the epithelial barrier integrity. Pathogens and their products (MAMPs, red stars) are also sensed by PRRs and induce MyD88- or inflammasome-dependent expression of a pro-inflammatory and antimicrobial program. In consequence, high levels of AMPs and cytokines/chemokines are produced that help limit pathogen propagation and contribute to the recruitment of immune cells. hBD, human β-defensin; mBD, mouse β-defensin; HD, human α-defensin.