title: Bacterial Pili exploit integrin machinery to promote immune activation and efficient blood-brain barrier penetration.
abstract: Group B Streptococcus (GBS) is the leading cause of meningitis in newborn infants. Bacterial cell surface appendages, known as pili, have been recently described in streptococcal pathogens, including GBS. The pilus tip adhesin, PilA, contributes to GBS adherence to blood-brain barrier (BBB) endothelium; however, the host receptor and the contribution of PilA in central nervous system (CNS) disease pathogenesis are unknown. Here we show that PilA binds collagen, which promotes GBS interaction with the α₂β₁ integrin resulting in activation of host chemokine expression and neutrophil recruitment during infection. Mice infected with the PilA-deficient mutant exhibit delayed mortality, a decrease in neutrophil infiltration and bacterial CNS dissemination. We find that PilA-mediated virulence is dependent on neutrophil influx as neutrophil depletion results in a decrease in BBB permeability and GBS-BBB penetration. Our results suggest that the bacterial pilus, specifically the PilA adhesin, has a dual role in immune activation and bacterial entry into the CNS.
authors: Department of Biology and Center for Microbial Sciences, San Diego State University, San Diego, California 92182, USA.
authors: Anirban
authors: A
authors: Banerjee
authors: Brandon J
authors: BJ
authors: Kim
authors: Ellese M
authors: EM
authors: Carmona
authors: Andrew S
authors: AS
authors: Cutting
authors: Michael A
authors: MA
authors: Gurney
authors: Chris
authors: C
authors: Carlos
authors: Ralph
authors: R
authors: Feuer
authors: Nemani V
authors: NV
authors: Prasadarao
authors: Kelly S
authors: KS
authors: Doran
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D001812:Blood-Brain Barrier; D018925:Chemokines / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D010861:Fimbriae, Bacterial; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D038982:Integrin alpha2beta1 / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism; D016920:Meningitis, Bacterial / Q000276:immunology / Q000382:microbiology; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D015398:Signal Transduction; D013292:Streptococcus agalactiae / Q000276:immunology / Q000502:physiology*
chemical_list: D018925:Chemokines; D038982:Integrin alpha2beta1; D016209:Interleukin-8; D051416:Focal Adhesion Protein-Tyrosine Kinases