Table 1.

Response of various components of the innate immune system to the intra-amniotic infection/inflammation.

Component of the innate immune system		Function	Response to the intra-amniotic infection
hAM as a physical barrier		Prevention of microbial entry	The presence of inflammatory mediators leads to the loss of tight junctions between the hAEC and an increased level of apoptosis, senescence and necrosis (84–92).
			The EMT transitions of hAEC can weaken the hAM and contribute to the onset of parturition (90–94).
			The endogenous host response to microbial infections includes secretion of extracellular matrix degrading enzymes matrix metalloproteinases (93, 95–106).
			The invading microbes may produce their own extracellular matrix-degrading enzymes (107).
			Loss of hAM’s integrity increases chances of PROM (90–92, 108–111).
Immune cells	Neutrophils	Production of reactive oxygen species that are cytotoxic to microbes, phagocytosis, production of antimicrobial peptides and cytokines	The hAF neutrophils can be predominantly of the fetal or maternal origin or a mixture of both (112, 113).
			The hAF neutrophils can invade the amniotic cavity, therefore, the fetus and the mother participate in the host defense mechanisms against intra-amniotic infection (113–118).
			The hAF neutrophils phagocytose bacteria and form neutrophil extracellular traps (113–115, 118).
	Monocytes/Macrophages	Production of nitric oxide that is cytotoxic to microbes, phagocytosis, production of cytokines	Monocytes/macrophages can be predominantly of the fetal or maternal origin or a mixture of both (119).
			Monocytes/macrophages in the amniotic cavity primarily act through the release of pro-inflammatory cytokines (120, 121).
Pattern recognition receptors (PRRs)	Toll-like receptors (TLRs)	Recognition of conserved features of microbes and downstream signaling	PRRs induce inflammation through the activation of several inflammatory pathways (122–131).
	Nucleotide-binding oligomerization domain (NOD)- Leucine-Rich Repeats (LRR)-containing receptors (NLRs)		Intra-amniotic infection leads to an increase of the transcriptional level of NLRP1, NLRP3, NLRC4, NOD2 (118).
	Retinoic acid-inducible gene 1 (RIG-1)-like receptors (RLRs)		Activation of the NLRP3 inflammasome promotes preterm birth (118, 132–138).
	C-type lectin receptors (CLRs)		TLR1-10 are expressed by the hAEC (122, 139).
Cytokines		Signaling molecules that mediate and regulate immunity, inflammation and hematopoiesis	Presence of IL-6, IL-1β, IL-10, IL-18, TNFα, macrophage migration inhibitory factor, nicotinamide phosphoribosyltransferase, TGFβ, granulocyte-macrophage colony-stimulating factor, high-mobility group protein 1, IL-10 and IL-6 in the hAF with IAI or preterm labor conditions (118, 121, 128, 129, 140–153).
			An elevated level of cytokines IL-1β, IL-6, TNFα, IFNγ, EGF, MIP3α in patients with PROM and intra-amniotic infection (154).
			The intra-amniotic infection leads to an increased level of cytokines and chemokines IL-1b, IL-6, IL-8, TNFα, IFNγ, EGF, MIP3α, MIP1α, Eotaxin, IL-16, IL-8, monocyte chemoattractant protein-1, chemokine (C-X-C motif) ligands (CXCLs)-1, -3, -4, -5, -6, -10, -11 and L-selectin (128, 146, 147, 154–159).
Antimicrobial peptides	α- and β-defensins	AMPs damage and kill bacteria mainly by disrupting their membrane	AMPs are expressed by the hAM cells and are present in the hAF (23, 160–176).
	SLPI		Intra-amniotic infection leads to increased levels of AMPs (23, 100–102, 150, 152, 162, 166, 168–174, 177–183).
	Elafin
	Calgranulin/Calprotectin
	Lactoferrin
	Lipocalin 2
	Cathelicidin
Lipids and derivatives	Prostaglandins	Bioactive molecules that mediate human parturition	Intra-amniotic infection leads to an increased prostaglandin-prostamide ratio (122, 139, 184–197).
	5-lipoxygenase pathway molecules		Intra-amniotic infection causes an increase of molecules of 5-lipoxygenase pathway (191, 198).
Complement system	Complement molecules C3a, Bb	Complement activation lyses pathogens and regulates innate and adaptive immune response	C3a and Bb are increased in the hAF of women with intra-amniotic infection (199, 200).
	Inhibitor CD-59
Other molecules and pathways	Glycolysis	Various - consequence of infection/inflammation or unknown	Upon intra-amniotic infection or inflammation numerous molecules show changed concentration in the hAF (102, 174, 178, 201–211).
	Gluconeogenesis
	Iron homeostasis
	Immune cell products
	Other