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Updated: Jun 19, 2025
Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages
Published on: April 20, 2018
Inflammation and Macrophage Loss Mark Increased Susceptibility in a Genetic Model of Acute Viral Infection-Induced
Jessica L Annis1,2, Michael G Brown1,2,3,4
1Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA.
Abstract:
M.R2k/b mice are identical to the MA/My parent strain aside from a 5.58-Mb C57L-derived region on chromosome 17 (Cmv5s) that causes increased susceptibility to acute murine CMV (MCMV) infection and the development of significant spleen tissue damage. Spleen pathology begins at the marginal zone (MZ), apparent by 2 d postinfection (dpi), and progresses throughout the red pulp by 4 dpi. To better understand how M.R2k/b mice respond to infection and how Cmv5s contributes to tissue damage in the spleen, we assessed the regulation of myeloid cells and inflammation during acute MCMV infection in MA/My and M.R2k/b mice. We found that Cmv5s drove increased neutrophil accumulation and cell death at the MZ, which corresponded with evidence of localized oxidative stress and increased overall spleen IL-6 and TGF-β1 early during infection. Further assessment of MCMV infection dynamics at the early MZ revealed infected SIGNR1+ MZ macrophages as the first apparent cell type lost during infection in these mice and the likely target of early neutrophil recruitment. Spleen macrophages were also identified as the mediators of differential spleen IL-6 and TGF-β1 between MA/My and M.R2k/b mice. Interrogation of MCMV progression past 2 dpi revealed substantial M.R2k/b F480+ red pulp macrophage loss along with buildup of oxidative stress and MZ macrophage debris that was not neutrophil dependent. Together we identify Cmv5s-driven macrophage loss and inflammation during acute MCMV infection corresponding with the spatial and temporal development of spleen tissue damage.
Insights
Genetic factors on chromosome 17 (Cmv5s) increase susceptibility to murine cytomegalovirus (MCMV) infection, leading to spleen damage. This study reveals Cmv5s drives myeloid cell loss and inflammation, causing spleen pathology.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Murine cytomegalovirus (MCMV) infection causes spleen pathology in susceptible mouse strains.
- A specific genetic region (Cmv5s) on chromosome 17 is linked to increased MCMV susceptibility and spleen damage.
Purpose of the Study:
- To investigate the role of Cmv5s in myeloid cell regulation and inflammation during acute MCMV infection.
- To understand how Cmv5s contributes to spleen tissue damage.
Main Methods:
- Comparative analysis of myeloid cell populations and inflammatory markers in MA/My and M.R2k/b mice during MCMV infection.
- Assessment of spleen pathology, including neutrophil accumulation, cell death, oxidative stress, and macrophage populations.
Main Results:
- Cmv5s significantly increased neutrophil accumulation and cell death at the spleen's marginal zone (MZ), correlating with oxidative stress and elevated IL-6 and TGF-β1.
- Infected SIGNR1+ MZ macrophages were the first cells lost, likely initiating neutrophil recruitment. Spleen macrophages mediated differential cytokine production.
- Beyond 2 days post-infection, significant F480+ red pulp macrophage loss occurred, independent of neutrophils, alongside debris accumulation.
Conclusions:
- Cmv5s drives early macrophage loss and inflammation in the spleen during MCMV infection.
- This Cmv5s-mediated immune response contributes to the observed spleen tissue damage.
- Understanding these mechanisms can inform strategies against MCMV-induced pathology.
