Immunomodulatory properties of characellide A on human peripheral blood mononuclear cells

Simone Marcella,A Louise Allcock,Stefania Loffredo,Olivier P Thomas,Paul V Murphy,Sam Afoullouss

doi:10.1007/s10787-021-00836-5

Abstract

Marine sponges and their associated microbiota are multicellular animals known to produce metabolites with interesting pharmacological properties playing a pivotal role against a plethora of pathologic disorders such as inflammation, cancer and infections. Characellide A and B belong to a novel class of glycolipopeptides isolated from the deep sea marine sponge Characella pachastrelloides. In this study, we have evaluated the effects of characellide A and B on cytokine and chemokine release from human peripheral blood mononuclear cells (PBMC). Characellide A induces a concentration- and time-dependent CXCL8, IL-6 and TNF-α release from PBMC. This production is mediated by the induction of gene transcription. Moreover, cytokine/chemokine release induced by characellide A from PBMC is CD1d-dependent because a CD1d antagonist, 1,2-bis(diphenylphosphino)ethane [DPPE]-polyethylene glycolmonomethylether [PEG], specifically inhibits characellide A-induced activation of PBMC. In conclusion, characellide A is a novel modulator of adaptative/innate immune responses. Further studies are needed to understand its potential pharmacological application.

Highlights

Marine sponges are sessile multicellular animals characterized by a soft and sessile body (Anjum et al 2016)
The production of TNF-α induced by characellide A was comparable to that of simplexide (10 μg/ml), our positive control, whereas the release of IL-6 and TNF-α was lower (Fig. 1A–C)
Polymyxin B did not influence the capacity of characellide A to induce the release of CXCL8, IL-6, and TNF-α, whereas it almost completely suppressed the production of cytokines and chemokines induced by LPS (Table 1)

Summary

Introduction

Marine sponges are sessile multicellular animals characterized by a soft and sessile body (Anjum et al 2016). CD1d is a MHC-like presenting antigen molecule, belonging to the CD1 family, expressed on immune cells including monocytes, macrophages, dendritic cells B lymphocytes, thymocytes but not mature T cells (Exley et al 2000; Brigl and Brenner 2004). Two metabolites belonging to a new class of glycolipopeptides, namely characellide A and B, were recently isolated from the deep sea marine sponge Characella pachastrelloides Both characellides were first shown to inhibit reactive oxygen species (ROS) production from microglia BV-2 cell line stimulated with Lipopolysaccharide (LPS), acting as anti-inflammatory mediators (Afoullouss et al 2019). We investigated the effects of characellides A and B on human peripheral blood mononuclear cells (PBMC) and we tried to understand their mechanism of action

Methods

Results

Conclusion