Scavenger receptors in host defense: from functional aspects to mode of action

Abstract

Scavenger receptors belong to a superfamily of proteins that are structurally heterogeneous and encompass the miscellaneous group of transmembrane proteins and soluble secretory extracellular domain. They are functionally diverse as they are involved in various disorders and biological pathways and their major function in innate immunity and homeostasis. Numerous scavenger receptors have been discovered so far and are apportioned in various classes (A-L). Scavenger receptors are documented as pattern recognition receptors and known to act in coordination with other co-receptors such as Toll-like receptors in generating the immune responses against a repertoire of ligands such as microbial pathogens, non-self, intracellular and modified self-molecules through various diverse mechanisms like adhesion, endocytosis and phagocytosis etc. Unlike, most of the scavenger receptors discussed below have both membrane and soluble forms that participate in scavenging; the role of a potential scavenging receptor Angiotensin-Converting Enzyme-2 has also been discussed whereby only its soluble form might participate in preventing the pathogen entry and replication, unlike its membrane-bound form. This review majorly gives an insight on the functional aspect of scavenger receptors in host defence and describes their mode of action extensively in various immune pathways involved with each receptor type. Video abstract.

Keywords: ACE-2; Immunity; PAMPs; Scavenger receptors; Signalling pathways.

Fig. 1

Schematic representation of various members of Types A Scavenger receptor: SR-A1, SR-A3, SR-A4, SR-A5, SR-A6. Various domains are shown in the key within the picture

Fig. 2

Schematic representation of SR-B receptor class shows interaction with TLR2/6 and TLR4 receptors. TLR2/6 binds to LTA of gram-positive bacteria and TLR4 on interaction with LPS of gram-negative bacteria shows activation of proinflammatory signaling cascade, SRC family kinases and MAPKs

Fig. 3

(a) LOX-1 on interaction with TLR2 on infection with PTX3 of Klebsiella Pneumonia shows OmpA internalization and stimulation of proinflammatory response. On binding to diverse microbial ligands it participates in antigen presentation on MHC class-I of dendritic cells in association with heat-shock protein HSP70. (b) Dectin-1 on binding to diverse antigens dimerize and activate CARD9, Bcl10, and MALT10, while on binding to TLR2/6 activates TRAF6, IRAK1, and IRAK4 leading to activation of proinflammatory cytokines and chemokines

Fig. 4

SCAR-F1 on binding to diverse ligands like B-glucans, OmpA, NS3 in presence of TLR2 activates proinflammatory response, Antigen cross-presentation and viral uptake. On interaction with TLR4 in presence of LPS it activates MAP kinases following activation of various transcriptional factors like p38 and JNK that mediate extracellular release of IL6, TNF-α and INF-β

Fig. 5

SCAR-G on immune cell activates various immune related pathways like Th1 immune response via activation of IL12 and IFN-γ. On binding to gram-negative and gram-positive bacteria this receptor activates phagocytosis of bacteria into mature APCs following activation of IL12, TNF-α and p40 that helps to convert Th0 into Th1 cells

Fig. 6

SR-J/RAGE interacts with TLR4 receptor in response to synergistic interaction between HMGB1-LPS complex in activating the macrophages through phosphorylation of MAPK p38 and activation of NF-κB following release to proinflammatory molecules like IL16, IL1-β and TNF-α

Fig. 7

Membrane bound ACE-2 receptor binds to the spike proteins on SARS-CoV-2, which helps in its internalization. However, soluble form of this receptor (sACE-2) acts a scavenger to prevent the internalization of virus by inhibiting the binding process