Related Experiment Video
Updated: Jul 5, 2025
Assessing Anti-fungal Activity of Isolated Alveolar Macrophages by Confocal Microscopy
Published on: July 9, 2014
A Functional Assessment of Fetal Liver and Monocyte-Derived Macrophages in the Lung Alveolar Environment
Wen Xuan Zhang1,2, Arpan Sharma Neupane1,2, Bruna Araujo David1,2
1Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Abstract:
It is becoming clear that every organ is seeded by a population of fetal liver-derived macrophages that are replaced at different rates by monocyte-derived macrophages. Using the Ms4a3tdTomato reporter mouse that reports on monocyte-derived alveolar macrophages (Mo-AMs) and our ability to examine AM function using our multichannel intravital microscopy, we examined the fetal-liver derived alveolar macrophage (FL-AM) and Mo-AM populations within the same mouse under various environmental conditions. The experiments unveiled that AMs migrated from alveolus to alveolus and phagocytosed bacteria identically regardless of ontogenic origin. Using 50 PFU of influenza A virus (IAV) determined using the Madin-Darby canine kidney (MDCK) cell line, we noted that both populations were susceptible to IAV-induced immunoparalysis, which also led to impaired phagocytosis of secondary bacterial infections. Both FL-AMs and Mo-AMs were trained by β-glucan to resist IAV-induced paralysis. Over time (40 wk), Mo-AMs began to outperform FL-AMs, although both populations were still sensitive to IAV. Our data also show that clodronate depletion of AMs leads to replenishment, but by FL-AMs, and these macrophages do show some functional impairment for a limited time. Overall, the system is designed such that new macrophages rapidly assume the function of tissue-resident macrophages when both populations are examined in an identical environment. These data do differ from artificial depletion methods that compare Mo-AMs and FL-AMs.
Insights
Fetal liver-derived and monocyte-derived macrophages function similarly in the lungs, but monocyte-derived macrophages improve over time. Both are susceptible to influenza A virus-induced paralysis, yet can be trained to resist it.
Area of Science:
- Immunology
- Cell Biology
- Respiratory Medicine
Background:
- Organs are populated by fetal liver-derived macrophages, later replaced by monocyte-derived macrophages.
- Alveolar macrophages (AMs) play a crucial role in lung immunity.
Purpose of the Study:
- To compare the function and behavior of fetal liver-derived AMs (FL-AMs) and monocyte-derived AMs (Mo-AMs) within the same mouse.
- To investigate the susceptibility of both AM populations to influenza A virus (IAV) and subsequent bacterial infections.
- To assess the impact of training (e.g., with β-glucan) and time on AM function.
Main Methods:
- Utilized the Ms4a3tdTomato reporter mouse to distinguish Mo-AMs.
- Employed multichannel intravital microscopy to examine AM function in vivo.
- Inoculated mice with influenza A virus (IAV) and assessed phagocytic activity and susceptibility to secondary bacterial infections.
Main Results:
- FL-AMs and Mo-AMs exhibited identical migration and phagocytosis of bacteria.
- Both AM populations were susceptible to IAV-induced immunoparalysis, impairing secondary bacterial clearance.
- β-glucan training conferred resistance to IAV-induced paralysis in both FL-AMs and Mo-AMs.
- Over 40 weeks, Mo-AMs showed improved performance compared to FL-AMs, though both remained sensitive to IAV.
- Clodronate depletion led to FL-AM replenishment, with transient functional impairment.
Conclusions:
- Newly recruited macrophages rapidly adopt the functions of tissue-resident macrophages in identical environments.
- AM ontogeny influences long-term function, with Mo-AMs outperforming FL-AMs over time.
- Understanding AM dynamics is crucial for developing effective immune strategies against respiratory infections.
More Related Videos
08:54In Vivo Assessment of Alveolar Macrophage Efferocytosis Following Ozone Exposure
Published on: October 22, 2019
07:21Processing of Bronchoalveolar Lavage Fluid and Matched Blood for Alveolar Macrophage and CD4+ T-cell Immunophenotyping and HIV Reservoir Assessment
Published on: June 23, 2019