title: Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.
abstract: 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(GFP/+) 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⁺ Ly6C(low) 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 Ly6C(high) and Ly6C(low) monocytes into infected mice, we found that AAM originate primarily from transferred Ly6C(high) monocytes, but that these cells may transition through a Ly6C(low) state and adopt patrolling behavior in the vasculature. Thus, during chronic helminth infection AAM can arise from recruited Ly6C(high) monocytes via help from CD4⁺ T cells.
authors: Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.
authors: Natasha M
authors: NM
authors: Girgis
authors: Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.
authors: Uma Mahesh
authors: UM
authors: Gundra
authors: Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.
authors: Lauren N
authors: LN
authors: Ward
authors: Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.
authors: Mynthia
authors: M
authors: Cabrera
authors: Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.
authors: Ute
authors: U
authors: Frevert
authors: Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.
authors: P'ng
authors: P
authors: Loke
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000097:blood* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D002450:Cell Communication; D054338:Cell Transdifferentiation; D003433:Crosses, Genetic; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007157:Immunologic Surveillance; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D010063:Ovum / Q000254:growth & development / Q000276:immunology; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology / Q000503:physiopathology; D015854:Up-Regulation
chemical_list: D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins