Related Experiment Video
Updated: Jun 28, 2026
Polarization of M1 and M2 Human Monocyte-Derived Cells and Analysis with Flow Cytometry upon Mycobacterium tuberculosis Infection
Published on: September 18, 2020
M1 Macrophage Polarization Prevails in Epstein-Barr Virus-Infected Children in an Immunoregulatory Environment
A Moyano1, N M Ferressini Gerpe1, E De Matteo2
1Multidisciplinary Institute for Investigation in Pediatric Pathologies (IMIPP), CONICET-GCBA. Molecular Biology Laboratory, Pathology Division, Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina.
Abstract:
Macrophages can be polarized toward a proinflammatory phenotype (M1) (CD68+) or to an anti-inflammatory one (M2) (CD163+). Polarization can be triggered by cytokines such as IFN-γ for M1, or IL-10 and TGF-β, for M2. In the context of pediatric Epstein Barr virus (EBV) infection, little is known about macrophage polarization in EBV primary or persistent infection. When studying tonsils of patients undergoing primary infection (PI), healthy carrier (HC), reactivation (R), and not infected (NI), M1 profile prevailed in all infection status. However, an increase in M2 cells was observed in those patients with broader expression of latency antigens, in particular EBNA2. Tonsils from primary infected patients showed an increased IL-10 expression, whereas, unexpectedly, TGF-β expression correlated with M1 marker. Furthermore, an inverse correlation was demonstrated between CD68 and IFN-γ. Therefore, in the context of asymptomatic infection in children, M1 macrophage polarization prevails, even in the presence of IL-10 and TGF-Ꞵ immunomodulatory cytokines, and it might be independent from lymphomagenesis process. Our finding indicates that macrophages may have a significant plasticity in response to different types of extrinsic stimuli, and further studies are required to investigate M1 polarization under anti-inflammatory stimuli. IMPORTANCE Most studies on Epstein Barr virus (EBV) primary infection have been performed in adolescents and young adult populations with Infectious Mononucleosis (IM) in developed countries. Furthermore, studies related to macrophage polarization were assessed in EBV-associated lymphomas, but little is known about macrophage polarization in the context of primary infection at the site of viral entry and replication, the tonsils. Therefore, the aim of this study was to characterize macrophage response in children undergoing EBV primary or persistent infection, in order to enlighten the role of macrophages in viral pathogenesis, in a population with a high incidence of EBV-associated lymphomas in children younger than 10 years old. This study may contribute to explain, at least in part, the asymptomatic viral infection in children from an underdeveloped region, given that M1 polarization pattern prevails, but in a regulatory environment.
Insights
In children with Epstein Barr virus (EBV) infection, M1 macrophage polarization is dominant, even with anti-inflammatory signals. This suggests macrophages are adaptable and may explain asymptomatic infections in children.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Macrophages exhibit plasticity, polarizing into proinflammatory (M1) or anti-inflammatory (M2) phenotypes.
- Little is known about macrophage polarization during pediatric Epstein Barr virus (EBV) infection, particularly at the site of entry (tonsils).
- Existing research often focuses on EBV-associated lymphomas or adolescent/adult populations with infectious mononucleosis.
Purpose of the Study:
- To characterize macrophage polarization in children with primary or persistent EBV infection.
- To investigate the role of macrophage polarization in pediatric EBV pathogenesis.
- To understand asymptomatic EBV infection in children from underdeveloped regions.
Main Methods:
- Analysis of tonsil tissues from children with primary infection (PI), healthy carriers (HC), reactivation (R), and uninfected (NI) status.
- Assessment of M1 (CD68+) and M2 (CD163+) macrophage markers.
- Evaluation of cytokine expression (IFN-γ, IL-10, TGF-β) and EBV latency antigens (EBNA2).
Main Results:
- The M1 macrophage profile was prevalent across all EBV infection statuses in children.
- Increased M2 cells correlated with broader expression of EBV latency antigen EBNA2.
- Primary EBV infection showed increased IL-10, while TGF-β unexpectedly correlated with M1 markers; CD68 inversely correlated with IFN-γ.
Conclusions:
- M1 macrophage polarization predominates in asymptomatic pediatric EBV infection, irrespective of immunomodulatory cytokines like IL-10 and TGF-β.
- Macrophage plasticity is evident in response to stimuli, suggesting M1 polarization may occur even under anti-inflammatory conditions.
- Further research is needed to explore M1 polarization under anti-inflammatory stimuli and its role in asymptomatic EBV infection and lymphomagenesis in children.
