Related Experiment Video
Updated: Apr 27, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Ly6C(high) monocytes become alternatively activated macrophages in schistosome granulomas with help from CD4+ cells
Natasha M Girgis1, Uma Mahesh Gundra1, Lauren N Ward1
1Department of Microbiology, New York University School of Medicine, New York, New York, United States of America.
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.
Insights
During chronic helminth infections, alternatively activated macrophages (AAM) are crucial. Our study shows these AAM primarily originate from recruited Ly6C-high monocytes, with CD4+ T cell assistance.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Alternatively activated macrophages (AAM) are key players in chronic T helper 2 inflammatory conditions.
- Liver granulomas, crucial for limiting parasite-induced tissue damage in Schistosoma mansoni infections, depend on AAM.
- The precise origin and dynamics of AAM during chronic helminth infections remain incompletely understood.
Purpose of the Study:
- To investigate the origin and dynamics of alternatively activated macrophages (AAM) in the liver during chronic Schistosoma mansoni infection.
- To characterize the role of monocyte subsets and CD4+ T cells in AAM accumulation within liver granulomas.
Main Methods:
- Utilized CX3CR1(GFP/+) reporter mice to track monocyte and macrophage populations in vivo.
- Employed intravital imaging to observe monocyte behavior around parasite eggs.
- Conducted adoptive transfer experiments with distinct monocyte subsets (Ly6C-high and Ly6C-low).
- Analyzed PD-L2 expression as a marker for AAM differentiation.
Main Results:
- CX3CR1-GFP+ monocytes and macrophages, expressing PD-L2 (indicating AAM differentiation), accumulated around Schistosoma mansoni eggs and within granulomas.
- Intravital imaging revealed altered patrolling behavior of Ly6C-low monocytes around eggs.
- Differential labeling demonstrated CD4+ T cell-dependent accumulation of PD-L2+ AAM in infected tissues.
- Adoptive transfer experiments indicated that Ly6C-high monocytes are the primary source of AAM, with potential transition through a Ly6C-low state.
Conclusions:
- Alternatively activated macrophages (AAM) in chronic helminth infection primarily arise from recruited Ly6C-high monocytes.
- CD4+ T cells play a critical role in facilitating the accumulation of these AAM within liver granulomas.
- Monocyte-derived AAM may transition through a Ly6C-low state and exhibit vascular patrolling behavior during infection.
More Related Videos
11:21Forward Genetics Screens Using Macrophages to Identify Toxoplasma gondii Genes Important for Resistance to IFN-γ-Dependent Cell Autonomous Immunity
Published on: March 12, 2015
11:31Targeting Drugs to Larval Zebrafish Macrophages by Injecting Drug-Loaded Liposomes
Published on: February 18, 2020
Related Concept Videos
01:12Chronic Inflammation: Introduction
01:25Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
01:28Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
01:15Differentiation of Common Myeloid Progenitor Cells
01:40Cell-mediated Immune Responses