Journal Article

monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells

Frevert, Ute, Gundra, Uma Mahesh, Loke, P'ng, Cabrera, Mynthia, Girgis, Natasha M, Ward, Lauren N

2014

Overview

Alternatively activated macrophages (AAM) that accumulate during chronic T helper 2 inflammatory conditions may arise through proliferation of resident macrophages or recruitment of monocyte-derived cells. Liver granulomas that form around eggs of the helminth parasite Schistosoma mansoni require AAM to limit tissue damage. Here, we characterized monocyte and macrophage dynamics in the livers of infected [CX3CR1.sup.GFP/+] mice. [CX.sub.3][CR1-GFP.sup.+] monocytes and macrophages accumulated around eggs and in granulomas during infection and upregulated PD-L2 expression, indicating differentiation into AAM. Intravital imaging of [CX.sub.3][CR1-GFP.sup.+] [Ly6C.sup.low] monocytes revealed alterations in patrolling behavior including arrest around eggs that were not encased in granulomas. Differential labeling of [CX.sub.3][CR1-GFP.sup.+] cells in the blood and the tissue showed [CD4.sup.+] T cell dependent accumulation of [PD-L2.sup.+] [CX.sub.3][CR1-GFP.sup.+] AAM in the tissues as granulomas form. By adoptive transfer of [Ly6C.sup.high] and [Ly6C.sup.low] monocytes into infected mice, we found that AAM originate primarily from transferred [Ly6C.sup.high] monocytes, but that these cells may transition through a [Ly6C.sup.low] state and adopt patrolling behavior in the vasculature. Thus, during chronic helminth infection AAM can arise from recruited [Ly6C.sup.high] monocytes via help from [CD4.sup.+] T cells.

• Publisher: Public Library of Science
• Subject: Health aspects / Helminthiasis / Immune response / Macrophages / Physiological aspects