Neonatal mice failed to induce an effective adaptive immune response to methicillin-resistant Staphylococcus aureus (MUC7P.773)

Abstract

Abstract The development of pneumonia in neonates due to infection by methicillin-resistant Staphylococcus aureus (MRSA) is associated with significant morbidity and mortality. Our lab has developed a neonatal mouse model of MRSA-induced pneumonia to investigate the pathogenesis of MRSA in neonates. Neonatal pups or adult mice were intranasally exposed to MRSA (USA300), and the pulmonary immune response was analyzed at various days post infection (dpi). We observed a decrease in the survival rate of neonates and an increase in bacterial load in the lungs of neonates in comparison to adult mice. The increase in bacterial load correlated with a decrease in the total number of cells in the bronchoalveolar lavage fluid, which corresponded to a decrease in macrophages and neutrophils in neonates compared to adults on 1dpi. By 6dpi, neonates failed to develop an effective Th1 response compared to the adults (1.3% CD4+/IFN-γ+ cells vs. 18% CD4+/IFN-γ+ cells). Also unlike the adults, neonates failed to mount a significant Th17 response (0.89% CD4+/IL-17+ vs. 2.6% CD4+/IL-17+). The failure of neonates to mount an efficient adaptive immune response correlated with a decrease in the frequency of DCs in the lung and with less mature DCs as determined by CD86 expression in comparison to adults. These studies suggest that the failure to induce a Th1 response in neonates results in their failure to control bacterial growth.