Immunological Insights into the Pathogenesis of Active CMV Infection in Non-Immunosuppressed Critically Ill Patients

Dissociation of cytomegalovirus (CMV) DNA loads between the lower respiratory tract and blood, with high levels in the former compartment and low or undetectable levels in the latter, commonly occurs during active CMV infection in critically ill patients despite the presence of high frequencies of CMV-specific IFN-γ-producing CD8+ and CD4+ T cells in blood. Data presented in this case report suggest that inter-compartmental differences in interleukin-10 (IL-10) levels may, in part, explain the pathobiology of this phenomenon. In the absence of ganciclovir treatment, a significant correlation was observed between IL-10 levels and CMV DNA loads in lower respiratory tract specimens (P= 0.016), but not in plasma samples (P = 0.46). Comparable data were obtained during the course of active CMV infection episodes that developed in six CMV-seropositive critically ill patients with no canonical immunosuppression. The presence of higher levels of IL-10 in the lower respiratory tract than in plasma may result in increased impairment of CMV-specific T-cell effector responses in the lung compared to the systemic compartment, facilitating local CMV replication.