Helminth-induced Ly6Chi monocyte-derived alternatively activated macrophages suppress experimental autoimmune encephalomyelitis

Cesar Terrazas,Lindsay M Webb,Stephanie A Amici,Miriam Rodriguez-Sosa,Hanna Cortado,Diana Martinez-Saucedo,Abhay R Satoskar,Mireia Guerau-De-Arellano,Steve Oghumu,Santiago Partida-Sánchez,Juan De Dios Ruiz-Rosado,Luis I Terrazas,Frank Robledo-Avila,Kyle A Jablonski

doi:10.1038/srep40814

Abstract

Helminths cause chronic infections and affect the immune response to unrelated inflammatory diseases. Although helminths have been used therapeutically to ameliorate inflammatory conditions, their anti-inflammatory properties are poorly understood. Alternatively activated macrophages (AAMϕs) have been suggested as the anti-inflammatory effector cells during helminth infections. Here, we define the origin of AAMϕs during infection with Taenia crassiceps, and their disease-modulating activity on the Experimental Autoimmune Encephalomyelitis (EAE). Our data show two distinct populations of AAMϕs, based on the expression of PD-L1 and PD-L2 molecules, resulting upon T. crassiceps infection. Adoptive transfer of Ly6C+ monocytes gave rise to PD-L1+/PD-L2+, but not PD-L1+/PD-L2− cells in T. crassiceps-infected mice, demonstrating that the PD-L1+/PD-L2+ subpopulation of AAMϕs originates from blood monocytes. Furthermore, adoptive transfer of PD-L1+/PD-L2+ AAMϕs into EAE induced mice reduced disease incidence, delayed disease onset, and diminished the clinical disability, indicating the critical role of these cells in the regulation of autoimmune disorders.

Highlights

Tissue resident macrophages originate before birth and acquire tissue specific phenotypes[5,6,7]
Our study shows that during experimental cysticercosis, Ly6Chi monocytes are recruited into the peritoneal cavity in a CCR2-dependent manner giving rise to AAMφs expressing programmed death-ligand 2 (PD-L2) and mannose receptor (MR)
An interesting study showed that during acute infection (

Summary

Introduction

Tissue resident macrophages originate before birth and acquire tissue specific phenotypes[5,6,7]. The comparative responses of tissue and blood-derived macrophages and the functional role of each macrophage subset during inflammation remain to be investigated. MS patients naturally infected with helminths had fewer relapses than uninfected patients, and elimination of the parasites worsened their condition[20,21] Despite these findings, the use of helminths as a therapy has a number of associated risks[13,22]. T. crassiceps-induced AAMφs, exhibited strong regulatory function on T cells and reversed the clinical signs of EAE in a mouse model. Together, these findings point to helminth-induced AAMφs as potential targets for the treatment of chronic inflammatory diseases

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Conclusion