Ly6Chigh Monocytes Become Alternatively Activated Macrophages in Schistosome Granulomas with Help from CD4+ Cells

PLoS Pathogens

Uma Mahesh Gundra¹  P'ng Loke¹  Mynthia Cabrera¹  Lauren N. Ward¹  Natasha M. Girgis¹  Ute Frevert¹ 

[1] Department of Microbiology, New York University School of Medicine, New York, New York, United States of America

关键词: Monocytes;    Granulomas;    Crawling;    Mice;    Schistosoma mansoni;    Sine waves;    Macrophages;    T cells;   

DOI  :  10.1371/journal.ppat.1004080

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 CX3CR1GFP/+ mice. CX3CR1-GFP+ monocytes and macrophages accumulated around eggs and in granulomas during infection and upregulated PD-L2 expression, indicating differentiation into AAM. Intravital imaging of CX3CR1-GFP+ Ly6Clow monocytes revealed alterations in patrolling behavior including arrest around eggs that were not encased in granulomas. Differential labeling of CX3CR1-GFP+ cells in the blood and the tissue showed CD4+ T cell dependent accumulation of PD-L2+ CX3CR1-GFP+ AAM in the tissues as granulomas form. By adoptive transfer of Ly6Chigh and Ly6Clow monocytes into infected mice, we found that AAM originate primarily from transferred Ly6Chigh monocytes, but that these cells may transition through a Ly6Clow state and adopt patrolling behavior in the vasculature. Thus, during chronic helminth infection AAM can arise from recruited Ly6Chigh monocytes via help from CD4+ T cells.

【 授权许可】

CC BY