Infant Immune Response to Bacterial Infection

Bacterial infection in preterm neonates is a significant clinical problem. Neutrophils play a critical role in the bactericidal process, which is immature in newborns though their peripheral blood neutrophil counts are similar to or higher than that of older children and adults. The use of steroids to enhance lung maturation in premature infants complicates this problem. Many studies have shown different biological activities between lipopolysaccharide (LPS) activated neonatal cord blood neutrophils and adult peripheral blood neutrophils. In spite of a number of previous studies, the genetic basis of this differential response to LPS-activation remains unknown. In this study, we will identify the differential gene expression profiles of LPS-activated adult peripheral blood versus cord blood neutrophils from both term and preterm infants by whole genome ligonucleotide microarray. We will investigate the priming effect of histologic chorioamnionitis (HCA), a severe infection/inflammation implicated in many neonatal diseases, on the immune response in neutrophils in terms of gene expression. The effect of prenatal administration of steroids on the immune response in preterm neutrophils is another question we will address in the proposed study. This study will provide insight into the molecular basis for genetic regulation of neutrophil development. We expect to identify novel genes with differential expressions in LPS-activated cord blood neutrophils when compared to those of LPS-activated adult cells. Aberrant transcripts due to the priming effect of HCA to the immune response in term neutrophils will also provide insight on the defense mechanism of subsequent exposures to bacterial infection.

This is a collaborative study. All samples will be collected by our Collaborators at the Chinese University of Hong Kong, Hong Kong. We will perform expression profiling in the Laboratory of Clinical Genomics at NICHD. This protocol has been approved by the Joint Clinical Research Ethics Committee of the Chinese University of Hong Kong and Hospital Authority of Hong Kong.