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Intermediate stages in monocyte-macrophage differentiation modulate phenotype and susceptibility to virus infection
K C McCullough1, S Basta, S Knötig
1Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland.
Abstract:
The kinetics of monocyte-macrophage differentiation was analysed using two Swine Workshop Cluster (SWC) CD molecules: SWC1 and SWC9. Myeloid cells were selected by labelling for the common myeloid antigen, SWC3. Confirmation of macrophage identification used acid phosphatase and phagocytosis activities. During differentiation, SWC1 was gradually lost. SWC9 was absent on monocytes but up-regulated early. Consequently, monocytes were SWC1+ SWC9- and macrophages were SWC1- SWC9+. An additional, intermediate, cell population was identified as SWC1+ SWC9+. Size and granularity characteristics mirrored the monocyte, macrophage and intermediate-cell phenotypes. Overall, SWC9 up-regulation was central in macrophage differentiation and dependent on plasma factors. The concomitant loss of SWC1 was independent of these factors, but always associated with mature macrophages. Upon up-regulation of SWC9, the SWC1+ SWC9+ intermediate monocytic cells became susceptible to African swine fever virus infection. These results demonstrate the heterogeneity of monocytic cell differentiation and the importance of these characteristics for interaction with monocytotropic viruses.
Insights
Monocyte-macrophage differentiation involves changes in Swine Workshop Cluster (SWC) molecules SWC1 and SWC9. SWC9 upregulation marks macrophage maturation, while SWC1 loss is associated with mature cells, impacting viral susceptibility.
Area of Science:
- Immunology
- Cell Biology
- Veterinary Science
Background:
- Monocyte-macrophage differentiation is a critical process in the immune system.
- Understanding cell surface markers is key to identifying and characterizing immune cell populations.
- Swine immune cells, particularly monocytes and macrophages, are crucial for understanding disease resistance.
Purpose of the Study:
- To analyze the kinetics of monocyte-macrophage differentiation using specific Swine Workshop Cluster (SWC) CD molecules.
- To identify and characterize intermediate cell populations during swine monocyte differentiation.
- To investigate the role of SWC molecules in the susceptibility of swine cells to viruses.
Main Methods:
- Selected myeloid cells using the common myeloid antigen SWC3.
- Utilized acid phosphatase and phagocytosis assays to confirm macrophage identification.
- Analyzed the expression of SWC1 and SWC9 molecules on monocytes, macrophages, and intermediate cells via flow cytometry.
Main Results:
- Monocytes were identified as SWC1+ SWC9-, while macrophages were SWC1- SWC9+.
- An intermediate cell population, SWC1+ SWC9+, was identified with distinct size and granularity.
- SWC9 upregulation, dependent on plasma factors, was central to macrophage differentiation, with concomitant SWC1 loss.
- SWC1+ SWC9+ cells showed increased susceptibility to African swine fever virus infection.
Conclusions:
- Monocyte-macrophage differentiation exhibits heterogeneity, characterized by distinct SWC marker expression.
- SWC9 upregulation is a key event in macrophage maturation, influencing cellular characteristics.
- The identified intermediate cell population plays a role in viral interactions, highlighting its importance in host-pathogen dynamics.