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Cytomegalovirus inhibits CD14 expression on human alveolar macrophages
H A Hopkins1, M M Monick, G W Hunninghake
1Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa College of Medicine, Iowa City, USA.
Abstract:
Cytomegalovirus (CMV) infection in transplant patients is associated with an increased incidence of gram-negative pneumonia; the mechanism for this is unknown. Human alveolar macrophages (HAM) are an important part of the response of the lung to gram-negative bacteria. They interact with lipopolysaccharide (LPS) via the surface receptor CD14. The effect of CMV on CD14 expression by HAM was examined. HAM were obtained from normal volunteers by bronchoalveolar lavage, and some were exposed to CMV. CD14 expression was assessed by immunofluorescent microscopy and flow cytometry. CMV inhibited the surface expression of CD14 on HAM. Release of soluble CD14 was also reduced from infected cells, and Northern blot analysis revealed that CD14 mRNA was reduced in CMV-exposed cells. These findings were specific for CD14 expression. These results demonstrate that CMV inhibits the ability of HAM to express CD14.
Insights
Cytomegalovirus (CMV) infection impairs human alveolar macrophages (HAM) by reducing CD14 expression. This impacts the lung
Area of Science:
- Immunology
- Virology
- Pulmonary Medicine
Background:
- Cytomegalovirus (CMV) infection in transplant patients correlates with increased gram-negative pneumonia.
- Human alveolar macrophages (HAM) are crucial for lung defense against gram-negative bacteria, interacting via the CD14 receptor.
- The mechanism linking CMV infection to impaired lung immunity remains unclear.
Purpose of the Study:
- To investigate the effect of Cytomegalovirus (CMV) on CD14 expression in human alveolar macrophages (HAM).
Main Methods:
- HAM were isolated from healthy volunteers via bronchoalveolar lavage.
- Cells were exposed to Cytomegalovirus (CMV) for experimental analysis.
- CD14 expression was quantified using immunofluorescent microscopy and flow cytometry.
- CD14 mRNA levels were assessed via Northern blot analysis.
Main Results:
- Cytomegalovirus (CMV) significantly inhibited the surface expression of CD14 on human alveolar macrophages (HAM).
- CMV infection led to reduced release of soluble CD14 from infected cells.
- Northern blot analysis confirmed a decrease in CD14 mRNA in CMV-exposed HAM, indicating transcriptional regulation.
- These inhibitory effects were specific to CD14 expression.
Conclusions:
- Cytomegalovirus (CMV) actively suppresses CD14 expression in human alveolar macrophages (HAM).
- This CMV-induced downregulation of CD14 may contribute to the increased susceptibility to gram-negative pneumonia observed in transplant patients.
- The findings highlight a novel mechanism by which CMV compromises innate immune responses in the lung.