The Scavenger Receptor SSc5D Physically Interacts with Bacteria through the SRCR-Containing N-Terminal Domain

Abstract

The scavenger receptor cysteine-rich (SRCR) family comprises a group of membrane-attached or secreted proteins that contain one or more modules/domains structurally similar to the membrane distal domain of type I macrophage scavenger receptor. Although no all-inclusive biological function has been ascribed to the SRCR family, some of these receptors have been shown to recognize pathogen-associated molecular patterns (PAMP) of bacteria, fungi, or other microbes. SSc5D is a recently described soluble SRCR receptor produced by monocytes/macrophages and T lymphocytes, consisting of an N-terminal portion, which contains five SRCR modules, and a large C-terminal mucin-like domain. Toward establishing a global common role for SRCR domains, we interrogated whether the set of five SRCR domains of SSc5D displayed pattern recognition receptor (PRR) properties. For that purpose, we have expressed in a mammalian expression system the N-terminal SRCR-containing moiety of SSc5D (N-SSc5D), thus excluding the mucin-like domain likely by nature to bind microorganisms, and tested the capacity of the SRCR functional groups to physically interact with bacteria. Using conventional protein–bacteria binding assays, we showed that N-SSc5D had a superior capacity to bind to Escherichia coli strains RS218 and IHE3034 compared with that of the extracellular domains of the SRCR proteins CD5 and CD6 (sCD5 and sCD6, respectively), and similar E. coli-binding properties as Spα, a proven PRR of the SRCR family. We have further designed a more sensitive, real-time, and label-free surface plasmon resonance (SPR)-based assay and examined the capacity of N-SSc5D, Spα, sCD5, and sCD6 to bind to different bacteria. We demonstrated that N-SSc5D compares with Spα in the capacity to bind to E. coli and Listeria monocytogenes, and further that it can distinguish between pathogenic E. coli RS218 and IHE3034 strains and the non-pathogenic laboratory E. coli strain BL21(DE3). Our work thus advocates the utility of SPR-based assays as sensitive tools for the rapid screening of interactions between immune-related receptors and PAMP-bearing microbes. The analysis of our results suggests that SRCR domains of different members of the family have a differential capacity to interact with bacteria, and further that the same receptor can discriminate between different bacteria strains and species.

Commentary: The Scavenger Receptor SSc5D Physically Interacts with Bacteria through the SRCR-Containing N-Terminal Domain

“…The recently published article by Bessa Pereira et al reports that the human SSc5D receptor physically interacts with some bacterial species (1), thus basically confirming previous available information on its mouse homolog (S5D-SRCRB) (2). The interspecies conservation of such a basic innate immune function (bacterial binding) has been noticed for other members of the scavenger receptor cysteine-rich superfamily (SRCR-SF) (e.g., human Spα and its mouse homolog AIM/Api6/CD5L) (3, 4).…”

Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu

“…Additionally, among common DEGs in stage I-II endometriosis, several of them are relative to inflammatory and/or infectious process. ZNF580 is potentially involved in the modulation of inflammatory process 141 ; DCAF15 is potentially involved in the immune surveillance 142 ; BANF1 is involved in the immunity against integration of foreign DNA and response to DNA damage 143 , and it is required to maintain undifferentiated phenotype of the stem cells 144 ; HECTD3 is associated to the modulation of host defense against infection 145 ; SSC5D, which is a soluble receptor produced by macrophages, T cells, and epithelial cells from placenta, is upregulated on infection and it has capacity to interact with bacteria 146 ; TEFB has a role in the autophagy and in the regulation of inflammasome 147 ; CD74 plays a role in the macrophage recruitment, adhesion and migration 148 . Despite the debatable utility of the biomarkers as noninvasive tool to diagnosis endometriosis 149,150 , these differences in transcript levels should be investigated further, at least as a driver to understand its pathophysiology.…”

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

“…It plays a role in the innate defence and homeostasis [188]. It binds to extracellular matrix proteins and acts as a pattern recognition receptor (PRR) by binding to pathogen-associated molecular patterns (PAMPs) present on the cell walls of bacteria and fungi, subsequently inhibiting PAMP-induced cytokine release [189]. It is implicated in arthritis [190].…”