2783. Expansion of Monocytic Myeloid-Derived Suppressor Cells in Infants with Severe Respiratory Syncytial Virus (RSV) Infection

Abstract

BackgroundRSV remains a leading cause for hospitalization of infants. The mechanisms associated with the ability of RSV to suppress the induction of an adequate immune response are not well understood and represent a challenge for vaccine development. Myeloid-derived-suppressor cells (MDSCs) have been shown to suppress CD8+ T cells in patients with malignancies. These immature myeloid cells are divided into three groups: granulocytic, monocytic, and undifferentiated. Of those, monocytic MDSCs (M-MDSCs) are considered to be key regulators of inflammatory responses during acute infections. Their potential role in the immunopathogenesis of RSV infection in infants is yet to be defined.MethodsSingle-center, prospective cohort study in previously healthy infants hospitalized with severe RSV lower respiratory tract infection (LRTI) and age-matched healthy controls (HC). Nasopharyngeal swabs for RSV detection and blood samples for cell immunophenotyping were analyzed at enrollment (D1), 1-month (D30), and 6-months (D180) follow-up visits. Disease severity was assessed using a clinical disease severity score (CDSS), duration of supplemental O2, and duration of hospitalization.ResultsWe enrolled 39 infants with RSV LRTI (median [IQR] age: 3.3 [1.5–5.2] months) and 5 HC (5.9 [4.5–7.2] months). Infants with RSV infection demonstrated an expansion of M-MDSCs during the acute infection (D1) that resolved to numbers comparable to those in HC at follow-up visits (Figure 1A). In addition, numbers of CD8+ T cells were significantly reduced during the acute infection (D1) in RSV-infected infants, but also returned to the HC baseline on D30 and D180 (Figure 1B). Finally, the increase in M-MDSCs numbers and decrease in CD8+ T-cell numbers were associated with worse clinical outcomes as defined by duration of supplemental oxygen (>1 day), hospitalization (>48 hours), and clinical disease severity score (CDSS, > 9) (Figure 2).ConclusionThese findings suggest that an expansion of M-MDSCs may play a role in T-cell suppression in children with severe RSV disease. As new vaccines are being developed, it is critical to elucidate the immune suppressive mechanisms associated with RSV infection. DisclosuresOctavio Ramilo, MD, Bill & Melinda Gates Foundation: Research Grant; Janssen: Research Grant; Merck: Advisory Board; NIH: Research Grant; Ohio Children’s Hospital Association (OCHA): Research Grant; Pfizer: Advisory Board, Consultant, Lectures; Sanofi/Medimmune: Advisory Board.