Um rápido estabelecimento da resposta imune prepara neonatos para a vida pós útero

Abstract

The liver plays an importance role in systemic homeostasis because it is involved in the elimination of microorganisms from the bloodstream. This is done especially by the continuous capture of bacteria by resident liver macrophages (Kupffer cells - KCs). In this context, bacteria that escape from the gastrointestinal system, as well as those that are disseminated through the bloodstream during systemic infections, are usually prevented from colonizing. In fact, liver diseases may predispose the patient to systemic spread of infections from different parts of the body. Nevertheless, the mechanisms involved in bacterial capture and elimination by the hepatic phagocytic system, and the chronology of maturation of the immune response during postnatal development are not relatively well known. The aim of this work was to characterize - using a combination of in vivo imaging, flow cytometry and gene analysis - the dynamics of bacterial systemic clearance during the different stages of murine development, as well as the cellular mechanisms used by Kupffer cells in capturing and eliminating of bacteria during this period. Our results demonstrated bacterial accumulation in the liver, following a single intravenous dose of Escherichia coli, which settles rapidly after inoculation (10-20 seconds). The majority of E. coli visualized in the liver were in intimate contact with KCs. Moreover, the effective elimination of liver and blood bacteria was correlated with a resistance to infection with high survival rates in adult mice. However, newborns had a low rate of capture of circulating bacteria, culminating in high counts of viable bacteria in the liver and increased post-infection mortality. Imaging by confocal intravital microscopy has revealed that KCs of neonates (up to 1 week post-birth) have a reduced capacity for capturing circulating bacteria, which can be explained by the reduced expression of genes involved in phagocytosis and bacterial death. Still, newborns had a lower rate of post-infection gene activation in relation to adults. Although it could be observed that animals at 1 week old had similar rates to adults for both capture and bacterial elimination, suggesting that despite initially deficient, the immune response to bacteria rapidly establishes in neonates. Taken together, our data provide a new picture of the bacterial / host interrelationship at different stages of development, suggesting that a relative postnatal hepatic immaturity may explain the high mortality during bacterial infections in newborns.