Migration of Myeloid Cells during Inflammation Is Differentially Regulated by the Cell Surface Receptors Slamf1 and Slamf8

Abstract

Previous studies have demonstrated that the cell surface receptor Slamf1 (CD150) is requisite for optimal NADPH-oxidase (Nox2) dependent reactive oxygen species (ROS) production by phagocytes in response to Gram- bacteria. By contrast, Slamf8 (CD353) is a negative regulator of ROS in response to Gram+ and Gram- bacteria. Employing in vivo migration after skin sensitization, induction of peritonitis, and repopulation of the small intestine demonstrates that in vivo migration of Slamf1-/- dendritic cells and macrophages is reduced, as compared to wt mice. By contrast, in vivo migration of Slamf8-/- dendritic cells, macrophages and neutrophils is accelerated. These opposing effects of Slamf1 and Slamf8 are cell-intrinsic as judged by in vitro migration in transwell chambers in response to CCL19, CCL21 or CSF-1. Importantly, inhibiting ROS production of Slamf8-/- macrophages by diphenyleneiodonium chloride blocks this in vitro migration. We conclude that Slamf1 and Slamf8 govern ROS–dependent innate immune responses of myeloid cells, thus modulating migration of these cells during inflammation in an opposing manner.

Putting Infection Dynamics at the Heart of Chagas Disease

“…Peripheral infection foci typically appear and disappear over the course of hours, consistent with trafficking of infected host cells [16]. Furthermore, in a fatal acute infection model, parasite burdens in the heart depended on the ability of T. cruzi to replicate specifically in myeloid cells expressing Slamf1 [98], a surface receptor with a pro-migratory function [99, 100]. Lastly, it is important to acknowledge the possibility that reinvasion may occur alongside reactivation of (quasi)dormant parasite foci.…”

Signalling lymphocyte activation molecule family member 9 is found on select subsets of antigen‐presenting cells and promotes resistance to Salmonella infection

“…All SLAM family receptors except for SLAMF9 have known ligands. CD48 and 2B4 interact heterotypically with one another, whereas SLAM, Ly9, CD84, NTB‐A, CRACC, and BLAME are homophilic. References to putative homotypic interactions by SLAMF9 are found in the literature, but the origins of this assumption are unclear, because no published data exist showing self‐association by SLAMF9.…”

“…Other SLAM family members without cytoplasmic ITSMs are able to signal without direct modification by tyrosine kinases. Although CD48 functions as the ligand for CD244 (2B4/SLAMF4), it can signal through its association with lipid rafts, and homotypic interactions by BLAME influence cellular function through unknown mechanisms …”

“…The best characterized functions of SLAM family receptors are their contributions to intercellular adhesion, leucocyte migration and cellular cytotoxicity . In addition to these functions, SLAM family receptors have been directly implicated in pathogen recognition and clearance by macrophages.…”

Diagnostic host gene signature for distinguishing enteric fever from other febrile diseases

“…While STAT1 and WARS are markers of an IFN‐γ response, SLAMF8 is a surface‐expressed protein (van Driel et al , ) found on macrophages, DCs and neutrophils and induced by IFN‐γ or Gram‐negative bacteria (Wang et al , ). SLAMF8 negatively regulates ROS production through inhibition of NADPH oxidase 2 (NOX2) in the bacterial phagosome and reduces ROS‐induced inflammatory cell migration (Wang et al , ). While oxidative stress is a common response to infection, Salmonella survival is reduced in SLAMF1‐deficient mice and can interfere with localization of functional NOX2 in Salmonella ‐containing vacuoles (SCVs), linking SLAM proteins and oxidative stress (Fang, ).…”