Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.

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 AA...

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Main Authors: Natasha M Girgis, Uma Mahesh Gundra, Lauren N Ward, Mynthia Cabrera, Ute Frevert, P'ng Loke
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-06-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC4072804?pdf=render
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author Natasha M Girgis
Uma Mahesh Gundra
Lauren N Ward
Mynthia Cabrera
Ute Frevert
P'ng Loke
author_facet Natasha M Girgis
Uma Mahesh Gundra
Lauren N Ward
Mynthia Cabrera
Ute Frevert
P'ng Loke
author_sort Natasha M Girgis
collection DOAJ
description 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.
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spelling doaj.art-8a68d44524744265978c833cd3ab82702022-12-22T00:13:14ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-06-01106e100408010.1371/journal.ppat.1004080Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.Natasha M GirgisUma Mahesh GundraLauren N WardMynthia CabreraUte FrevertP'ng LokeAlternatively 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.http://europepmc.org/articles/PMC4072804?pdf=render
spellingShingle Natasha M Girgis
Uma Mahesh Gundra
Lauren N Ward
Mynthia Cabrera
Ute Frevert
P'ng Loke
Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.
PLoS Pathogens
title Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.
title_full Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.
title_fullStr Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.
title_full_unstemmed Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.
title_short Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells.
title_sort ly6c high monocytes become alternatively activated macrophages in schistosome granulomas with help from cd4 cells
url http://europepmc.org/articles/PMC4072804?pdf=render
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AT laurennward ly6chighmonocytesbecomealternativelyactivatedmacrophagesinschistosomegranulomaswithhelpfromcd4cells
AT mynthiacabrera ly6chighmonocytesbecomealternativelyactivatedmacrophagesinschistosomegranulomaswithhelpfromcd4cells
AT utefrevert ly6chighmonocytesbecomealternativelyactivatedmacrophagesinschistosomegranulomaswithhelpfromcd4cells
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