Page 54 - MI-2-2

Microbes & Immunity

PERSPECTIVE ARTICLE
SRCR proteins uncovered: Their crucial role in

inflammation

Maria Carolina Silva 1† , Rita P. Pinto 1,2† , Liliana Oliveira 1,3 ,
and Alexandre M. Carmo *
1,3
1 i3S - Institute for Research and Innovation in Health, University of Porto, Porto, Portugal
2 Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
3 Institute of Molecular and Cell Biology, University of Porto, Porto, Portugal

Abstract

The scavenger receptor cysteine-rich (SRCR) superfamily comprises a highly conserved
group of extracellular soluble and membrane-attached glycoproteins that function as
pattern recognition receptors against a diverse range of pathogenic determinants.
While considerable attention has been devoted to their roles in microbial recognition,
this perspective aims to emphasize the significant, yet previously overlooked, anti-
inflammatory properties of circulating SRCR proteins, which may be even more
crucial for immune regulation. In addition, we examine SRCR cell surface proteins
† These authors contributed equally that, despite exhibiting limited microbial recognition, have demonstrated potential
to this work. in mitigating inflammation through their soluble forms released during infectious
*Corresponding author: and inflammatory conditions. Collectively, the paper emphasizes the dual roles of
Alexandre M. Carmo these proteins in infection control and the regulation of inflammatory responses,
(acarmo@i3s.up.pt) spotlighting their therapeutic potential in managing inflammatory diseases and
Citation: Silva MC, Pinto RP, enhancing host defense mechanisms.
Oliveira L, Carmo AM. SRCR
proteins uncovered: Their crucial
role in inflammation. Microbes & Keywords: Scavenger receptors; Pattern recognition receptors; Inflammation; Microbial
Immunity. 2025;2(2):46-52.
doi: 10.36922/mi.5741 recognition; Immune homeostasis
Received: November 1, 2024
Revised: December 20, 2024
1. Introduction
Accepted: January 6, 2025
The scavenger receptor cysteine-rich (SRCR) superfamily is primarily known for its
Published online: January 17,
2025 ability to recognize and bind various endogenous ligands, including lipids, proteins, and
carbohydrates, while also serving as pattern recognition receptors (PRRs) that identify
Copyright: © 2025 Author(s).
This is an Open-Access article microbial components to initiate immune responses and enhance innate immunity
distributed under the terms of the against infections. Among the various members of the SRCR superfamily, several have
1
Creative Commons Attribution distinct binding characteristics toward particular microbes. CD5 antigen-like (CD5L)
License, permitting distribution,
and reproduction in any medium, and soluble scavenger protein with 5 SRCR domains (SSC5D), which contain three and
provided the original work is five SRCR domains, respectively, are known to recognize pathogen-associated molecular
properly cited. patterns (PAMPs) from Gram-positive and Gram-negative bacteria, as well as pathogenic
Publisher’s Note: AccScience and saprophytic fungal species, promoting the aggregation of these microorganisms to
Publishing remains neutral with limit their dissemination. SSC4D, composed of four SRCR domains, engages directly
2-4
regard to jurisdictional claims in
published maps and institutional with various Gram-negative and Gram-positive bacterial species and also several
5
affiliations. protozoan parasites. Finally, deleted in malignant brain tumors 1 (DMBT1), a secreted

Volume 2 Issue 2 (2025) 46 doi: 10.36922/mi.5741