title: gp96 expression in neutrophils is critical for the onset of Escherichia coli K1             (RS218) meningitis.
abstract: Despite the fundamental function of neutrophils (polymorphonuclear leukocytes (PMNs))                 in innate immunity, their role in Escherichia coli K1 (EC-K1) -induced                 meningitis is unexplored. Here we show that PMN-depleted mice are resistant to EC-K1                 (RS218) meningitis. EC-K1 survives and multiplies in PMNs for which outer membrane                 protein A (OmpA) expression is essential. EC-K1 infection of PMNs increases the cell                 surface expression of gp96, which acts as a receptor for bacterial entry.                 Suppression of gp96 expression in newborn mice prevents the onset of EC-K1                 meningitis. Infection of PMNs with EC-K1 suppresses oxidative burst by                 downregulating rac1, rac2 and gp91(phox) transcription                 both in vitro and in vivo. The interaction of loop 2 of OmpA with gp96                 is essential for EC-K1-mediated inhibition of oxidative burst. These results reveal                 that EC-K1 exploits surface-expressed gp96 in PMNs to prevent oxidative burst for                 the onset of neonatal meningitis.
authors: Division of Infectious Diseases, Department of Pediatrics,                     The Saban Research Institute, Children's Hospital Los Angeles,                     Los Angeles, California                 90027, USA.
authors: Rahul
authors: R
authors: Mittal
authors: Nemani V
authors: NV
authors: Prasadarao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D016920:Meningitis, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism* / Q000382:microbiology*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C053387:endoplasmin