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

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

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


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.

Original languageEnglish (US)
Article numbere1004080
JournalPLoS pathogens
Issue number6
StatePublished - Jun 2014

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology


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