RESUMO
The polymeric immunoglobulin receptor (pIgR) plays a crucial role in mucosal immunity against microbial infection by transporting polymeric immunoglobulins (pIg) across the mucosal epithelium. We report here that the human pIgR (hpIgR) can bind to a major pneumococcal adhesin, CbpA. Expression of hpIgR in human nasopharyngeal cells and MDCK cells greatly enhanced pneumococcal adherence and invasion. The hpIgR-mediated bacterial adherence and invasion were abolished by either insertional knockout of cbpA or antibodies against either hpIgR or CbpA. In contrast, rabbit pIgR (rpIgR) did not bind to CbpA and its expression in MDCK cells did not enhance pneumococcal adherence and invasion. These results suggest that pneumococci are a novel example of a pathogen co-opting the pIg transcytosis machinery to promote translocation across a mucosal barrier.
Assuntos
Proteínas de Bactérias , Células Epiteliais/microbiologia , Mucosa Nasal/microbiologia , Infecções Pneumocócicas/metabolismo , Receptores de Superfície Celular , Receptores Acoplados a Proteínas G , Receptores de Imunoglobulina Polimérica/metabolismo , Streptococcus pneumoniae/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos , Aderência Bacteriana/fisiologia , Linhagem Celular , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Proteínas de Ligação a DNA/metabolismo , Células Epiteliais/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/imunologia , Proteínas de Choque Térmico/metabolismo , Humanos , Rim/citologia , Fígado/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microesferas , Dados de Sequência Molecular , Mucosa Nasal/citologia , Mucosa Nasal/imunologia , Faringe/citologia , Faringe/imunologia , Faringe/microbiologia , Glicoproteínas da Membrana de Plaquetas/química , Glicoproteínas da Membrana de Plaquetas/metabolismo , Ligação Proteica/fisiologia , Estrutura Terciária de Proteína , Coelhos , Receptores de Imunoglobulina Polimérica/química , Receptores de Imunoglobulina Polimérica/genéticaRESUMO
Changes in auditory brainstem responses (ABR) were studied and followed in hyperbilirubinemic newborns before and after exchange transfusion (ET), in order to check their usefulness in the early detection of acute and chronic bilirubin encephalopathy. ABR were measured in 10 newborns with marked hyperbilirubinemia (total bilirubin concentration [TBC] > or = 20 mg/dL, direct bilirubin concentration < 2 mg/dL) before and after ET. The means of birthweight, gestational age, and day of life on admission were 3267 g, 38.2 weeks and 3.4 days, respectively. The ABR measurements were performed before ET and 6.0 days (the mean) after the ET. The follow-up of ABR was performed at 3 months of life. In comparison with the control values, the mean latencies of ABR were significantly prolonged (I, I-III, and I-V: P < 0.05) and the mean amplitudes were significantly decreased (I, III and V: P < 0.001) before ET. Significant improvement of ABR was noticed after the ET, especially in the shortening of the latency of wave I (P < 0.02) and in increasing the amplitudes of wave III and V (P < 0.02 and (P < 0.01, respectively), though the recovery of the latency of I-V (P < 0.02) and the amplitudes of I, III and V wave (P < 0.001, P < 0.001 and P < 0.01, respectively) were delayed in comparison to the control. The follow-up data of ABR showed that, in two of nine infants (one was lost from the follow-up), there were still abnormal findings at 3 months of age. Only one of these, who prolonged the recovery of ABR until 5 years of age, developed a border intelligence. Though ET is effective for improvement of acute bilirubin encephalopathy with impaired ABR, a complete recovery of the ABR might be delayed in marked hyperbilirubinemia. The delay in improvement of ABR abnormalities might be possibly used as an early predictor for following chronic bilirubin encephalopathy.
