Helminth-induced Ly6C^hi monocyte-derived alternatively activated macrophages suppress experimental autoimmune...

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.