Characterization of innate lymphoid cells in infants with human cytomegalovirus infection

BACKGROUND: Human cytomegalovirus (HCMV) infection has a high global incidence and causes clinical symptoms including hepatitis, pneumonia, and infectious mononucleosis in children. While HCMV infection reshapes the host immune system, early-life alterations in innate lymphoid cells (ILCs) remain unelucidated. Therefore, this study investigated the percentages of total ILCs (TILCs) and ILC subsets, along with their correlations with clinical characteristics, in HCMV-infected infants. METHODS: After excluding other infections, malignancies, autoimmune diseases, or immunodeficiencies, 49 infants including 32 infants with HCMV infection and 17 HCMV-negative controls were enrolled. HCMV DNA levels were measured using PCR, and total ILCs as well as ILC subset proportions were determined by flow cytometry in blood samples. Demographic and clinical characteristics were extracted from the Laboratory Information Management System (LIS) and Hospital Information System (HIS). Chi-square and Mann‒Whitney U tests were used to compare demographic distribution and clinical characteristics between groups. Spearman correlation analysis was used to assess the correlations of clinical characteristics with total and ILC subset proportions. RESULTS: Based on HCMV DNA levels, 17 infants were assigned to the HCMV─ group (< 400 copies/mL) and 32 infants to the HCMV+ group (median 6140 copies/mL, IQR 1872.5–23,725). Flow cytometry revealed a significantly decreased percentage of ILC1s in HCMV+ infants (median 0.26, IQR 0.16–0.51) compared to HCMV− infants (median 0.55, IQR 0.33–1.035; p = 0.008). The proportion of ILC2s was lower in female infants (median 0.16, IQR 0.0615–0.2975) than in males (median 0.25, IQR 0.145–0.79). Within the HCMV+ group, females showed lower proportions and numbers of TILCs and ILC2s, compared to males. Additionally, within the HCMV+ group, the proportion of ILC1s was negatively correlated with AST (rₛ = -0.408, p = 0.038). CONCLUSIONS: The proportion of ILC1s was dramatically decreased in infants with HCMV infection and was negatively correlated with liver injury. The percentages of ILC2s and ILC3s in female infants with HCMV infection were lower than those in male infants. Therefore, the sex-specific effects of HCMV infection on the number and function of ILCs should be further investigated.