Scavenger receptors and β-glucan receptors participate in the recognition of yeasts by murine macrophages

TLDR

Macrophage recognition of fungi involves many receptors, notably β‑glucan receptor dectin‑1, but the role of scavenger receptors and how yeast binding differs in resting versus CpG‑ODN‑pre‑exposed macrophages remains poorly understood. The study aimed to determine how scavenger receptors contribute to uptake of zymosan and Candida albicans and to zymosan‑induced H₂O₂ production in macrophages. Using competitive ligands, transfected cells, and receptor‑deficient macrophages, the authors showed that untreated J774 cells internalize zymosan roughly equally via scavenger receptors and a β‑glucan receptor distinct from dectin‑1, the latter not driving H₂O₂ production. Scavenger receptors, especially class A SRs such as MARCO and SR‑A/CD204, redundantly mediate yeast uptake and zymosan‑induced H₂O₂ production, with CpG‑ODN pretreatment shifting the balance toward SRs and inhibition of β‑glucan receptors or SRs reducing Candida albicans uptake.

Abstract

Numerous receptors have been implicated in recognition of pathogenic fungi by macrophages, including the β-glucan receptor dectin-1. The role of scavenger receptors (SRs) in anti-fungal immunity is not well characterized.We studied uptake of unopsonized Saccharomycetes cerevisiae (zymosan) and live Candida albicans yeasts as well as zymosan-stimulated H(2)O(2) production in J774 macrophage-like cells and peritoneal exudate macrophages (PEMs). The role of different receptors was assessed with the use of competitive ligands, transfected cells and receptor-deficient macrophages.The uptake of zymosan by untreated J774 cells was mediated approximately half by SRs and half by a β-glucan receptor which was distinct from dectin-1 and not linked to stimulation of H(2)O(2) production. Ligands of β-glucan receptors and of SRs also inhibited uptake of C. albicans by macrophages (J774 cells and PEMs). In macrophages pretreated with a CpG motif-containing oligodeoxynucleotide (CpG-ODN) the relative contribution of SRs to yeast uptake increased and that of β-glucan receptors decreased. Whereas the class A SR MARCO participated in the uptake of both zymosan and C. albicans by CpG-ODN-pretreated, but not untreated macrophages, the related receptor SR-A/CD204 was involved in the uptake of zymosan, but not of C. albicans. The reduction of zymosan-stimulated H(2)O(2) production observed in DS-pretreated J774 cells and in class A SRs-deficient PEMs suggest that class A SRs mediate part of this process.Our results revealed that SRs belong to a redundant system of receptors for yeasts. Binding of yeasts to different receptors in resting versus CpG-ODN-pre-exposed macrophages may differentially affect polarization of adaptive immune responses.