Neonatal susceptibility to severe bacterial infections appears to be related to the complex interaction(s) of both host & bacteria. Little is known to account for either the unique bacterial spectrum or the predisposing factors resulting in these infections. The present study examines maturational determinants of the microbial-host cell interaction (MHCI) by evaluating non-opsonic adherence, invasiveness & cytotoxicity of group B streptococci (GBS), Listeria monocytogenes (L. mono) & Escherichia coli (E. coli), the bacteria responsible for 60% of these severe infections in the newborn (NB). These studies used target and phagocytic cells of varying maturational ages, i.e., tissue culture cell lines of 1) human skin fibroblasts from 1, 7 & 30 day old infants; 2) fetal & adult lung fibroblasts; as well as peripheral blood polymorphonuclear leukocytes (PMN) & monocytes from normal NB & adults. Although no age-related differences were seen in bacterial adherence to either cell type, invasiveness of the organisms was greater for cells from the NB infants compared to those from 30 day old & adults. GBS & E. coli exhibited greater invasiveness of skin fibroblasts from 1 day old infants, p<0.05& fetal lung fibroblasts. Using PMN & monocyte monolayers from 18 NB& 6 adults results showed similar adherence to all cell types by L. mono & E. coli. In contrast, there was significantly less adherence of GBS to cells from NB, p<0.001. Although L. mono was cytotoxic to cells from both NB & adults,GBS & E. coli were only cytotoxic to PMN & monocyte from NB, p<0.05. The cytotoxic factors were associated with the supernatants from both logarithmic & stationary growth of organisms. The cytotoxic factors from both GBS & L. mono significantly inhibited (>50%) adult phagocytic cell adherence (p<0.05), i.e.,GBS inhibited PMNs & L. mono inhibited monocytes. In addition, whole washed suspensions of L. mono were cytotoxic to both PMNs & monocytes from adults at 37°C but not at 4°C suggesting the active production of a cytolysin. No such cytolysin was produced by GBS or E. coli at either temperature. Collectively, these studies suggest that examination of the MHCI may be vital in the total assessment of NB susceptibility to infection and may provide new strategies for therapeutic interventions.
