EBV Impact in Peripheral Macrophages' Polarization Cytokines in Pediatric Patients

Macrophages are exceptionally flexible cells. The presence of inflammatory cytokines such as IFN-gamma and TNF-alpha results in an M1 (CD68) activation, while cytokines such as IL-10 or TGF-beta induce the M2 (CD163) activation. Our aim was to study the behavior of peripheral cytokines involved in macrophage polarization and relate them with tissue findings to further comprehend the role of macrophages in EBV pediatric infection. We studied cytokine expression in tonsils and peripheral blood samples of children in different stages of infection. Peripheral cytokines were compared with macrophage polarization markers and viral protein expression in tonsils. Only IL-10 showed a negative correlation between compartments, exclusively in patients undergoing viral reactivation (R). Higher expressions of peripheral IL-1 beta, IL-23, and IL-12p40 in R children were observed. Lower expressions of local and peripheral TNF-alpha in patients with broader expressions of latent and lytic viral proteins were demonstrated. In healthy carrier (HC) patients, IL-23 positively correlated with CD163, and IP-10 positively correlated with CD68. Our results indicated that EBV might modulate antigen expression in the presence of TNF-alpha and influence peripheral cytokine expression differently in each stage of infection. Moreover, peripheral cytokines might have a particular role in macrophage polarization in HC.