Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

Huang, Qianrui; Le, Yue; Li, Shusheng; Bian, Yi

doi:10.1186/s12931-024-02678-5

Respiratory Research

Table 1 ARDS related PRRs and non-PRRs, their lung tissue distribution and recognition of PAMPs and DAMPs

From: Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

Family	Member	Distribution	PAMPs	DAMPs
TLRs	TLR1	AECs, AMs, neutrophils	Triacyl lipopeptides	?
	TLR2	AECs, AMs, pulmonary endothelial cells, neutrophils	Diacyl lipopeptides, lipoteichoic acids	Histones, HMGB1, oxidized phospholipids
	TLR3	AECs	Viral dsRNA	Messenger RNA
	TLR4	AECs, AMs, neutrophils, pulmonary endothelial cells	LPS	Fibrinogen, HMGB1, hyaluronan, oxidized lipoproteins, phospholipids, histones, heat shock proteins
	TLR5	AECs, neutrophils	Flagellin	?
	TLR6	AECs, AMs, neutrophils	Bacterial lipopeptides	?
	TLR7	AECs, DCs, neutrophils	Microbial ssRNA	Host DNA fragments, microRNAs
	TLR8	AECs, neutrophils	Microbial ssRNA	Host DNA fragments, microRNAs
	TLR9	AECs, DCs, neutrophils	Microbial CpG-DNA	Host DNA fragments, microRNAs, mitochondrial CpG-DNA
NLRs	NOD1	Widely expressed	Peptidoglycan	?
	NOD2	AECs, leukocytes	Muramyl dipeptide, ssRNA	?
	NLRP1	AECs, leukocytes	Muramyl dipeptide	?
	NLRP3	AECs, immune cells, pulmonary endothelial cells	Microbial pore-forming toxins, microbial DNA or RNA, muramyl dipeptide	ATP, Ca²⁺ influx, hyaluronan, K⁺ efflux, oxidized mitochondrial DNA, ROS, uric acid,
	NLRC4	AMs	Flagellin	?
	NAIP	AECs, AMs	Flagellin	?
RLRs	RIG-I	Widely expressed	5’ triphosphate RNA	?
RLRs	MDA5	Widely expressed	5’ triphosphate RNA	?
CDSs	cGAS	Widely expressed	Microbial dsDNA	Self-DNA
CDSs	AIM2	Innate immune cells	Microbial dsDNA	Self-DNA, NETs
RAGE	RAGE	Widely expressed	LPS, microbial DNA, viral and parasitic proteins	HMGB1, S100 family
Non-PRRs	P2X7	Alveolar type I cells	–	ATP
	TRP channels	AECs, immune cells, pulmonary endothelial cells	Environmental irritants	Environmental irritants
	FPR	AECs, neutrophils	N-formylated peptides	N-formylated peptides

“?” in the table indicates the absence of information regarding the corresponding DAMPs or PAMPs recognized by the receptors, and “–” indicates no available information
AECs, alveolar epithelial cells; AIM2, absent in melanoma 2; AMs, alveolar macrophages; CDCs, cytoplasmic DNA sensors; cGAS, cyclic GMP-AMP synthase; DAMPs, damage-associated molecular patterns; DCs, dendritic cells; dsRNA, double-stranded RNA; FPR, N-formyl peptide receptor; HMGB1, high-mobility group box 1; LPS, lipopolysaccharide; MDA5, melanoma differentiation-associated gene 5; NAIP, neuronal apoptosis inhibitory protein; NETs, neutrophil extracellular traps; NLRs, nucleotide-binding leucine-rich repeat receptors; NLRC4, nucleotide-binding oligomerization domain like receptor subfamily C 4; NLRP, nucleotide-binding domain leucine-rich repeat protein; NOD, nucleotide-binding oligomerization domain; PAMPs, pathogen-associated molecular patterns; RAGE, receptor for advanced glycation end product; RIG-I, retinoic acid-inducible gene-I; RLRs, RIG-like receptors; ROS, reactive oxygen species; TLR, toll-like receptor; TRP, transient receptor potential

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ISSN: 1465-993X

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