(628) Myeloid-Derived Suppressor Cells (MDSC) Are Expanded in Pediatric Lower Respiratory Tract Infection

Introduction: Viral lower respiratory tract infections (LRTI) are a major cause of mortality in young children worldwide. Recent data suggest that severe LRTI is associated with T-cell suppression, though the mechanisms of suppression remain unknown. MDSC are immature, heterogenous cells that expand under inflammatory conditions and potently suppress T-cells, contributing to host immunosuppression. We hypothesized that MDSC expansion is associated with immunosuppressive T-cell profiles and increased disease severity in children with viral LRTI.

Methods: We conducted a prospective observational study of children < 5 yrs admitted to the PICU with viral LRTI. Children presenting for outpatient, elective procedures were enrolled as healthy controls. Disease severity was defined by level of respiratory support. We isolated peripheral blood mononuclear cells (PBMC) from whole blood and MDSC (CD45+, HLA-DR-, CD33+ and CD11b+), including G-(CD15+), M-MDSC (CD14+) subsets, and T-cell populations were identified by flow cytometry. Clinical data were collected from electronic medical records. Data represent median (IQR). Comparisons were made using the Mann-Whitney test.

Results: We enrolled 97 children: 44 LRTI (17 [9,45] mos; 55% male) and 53 HC (16 [10,28] mos, 77% male). 24 (55%) LRTI subjects were +rhino/enterovirus and 18 (41%) were +RSV. LRTI subjects had greater %MDSC of PBMC compared to HC (12% [5,23] v 6.4% [4.5,10] respectively, p=0.006). Both cohorts demonstrated M-MDSC predominance (91% [86,96] v 94% [88,97], p=0.2). LRTI subjects had decreased proinflammatory CD4+ Th17 and Th1 cells compared to HC (0.88% [0.35,1.6] v 1.3% [0.91,1.9], p=0.02) and (2.2% [1,3.5] v 3.4% [2.6,5.3], p=0.0002), respectively. LRTI subjects requiring non-invasive/invasive mechanical ventilation (MV) had higher %MDSC compared to high-flow or simple nasal cannula (NC) (16% [5.2,24] vs 7.7% [4.4,12], p=0.06).

Conclusions: Children critically ill due to viral LRTI demonstrated greater %MDSC compared to HC, and those requiring non-invasive/invasive MV had higher %MDSC compared to those requiring NC. The LRTI cohort demonstrated more immunosuppressive T-cell profiles compared to HC. Future studies are needed to confirm MDSC as a key mediator of T-cell suppression in pediatric LRTI and determine future mechanistic targets.