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Intravital Imaging of Vascular Transmigration by the Lyme Spirochete: Requirement for the Integrin Binding Residues of the B. burgdorferi P66 Protein. PLoS Pathog 2015 Dec;11(12):e1005333 PMID: 26684456 PMCID: PMC4686178

Pubmed ID

26684456

DOI

10.1371/journal.ppat.1005333

Abstract

Vascular extravasation, a key step in systemic infection by hematogenous microbial pathogens, is poorly understood, but has been postulated to encompass features similar to vascular transmigration by leukocytes. The Lyme disease spirochete can cause a variety of clinical manifestations, including arthritis, upon hematogenous dissemination. This pathogen encodes numerous surface adhesive proteins (adhesins) that may promote extravasation, but none have yet been implicated in this process. In this work we report the novel use of intravital microscopy of the peripheral knee vasculature to study transmigration of the Lyme spirochete in living Cd1d-/-mice. In the absence of iNKT cells, major immune modulators in the mouse joint, spirochetes that have extravasated into joint-proximal tissue remain in the local milieu and can be enumerated accurately. We show that BBK32, a fibronectin and glycosaminoglycan adhesin of B. burgdorferi involved in early steps of endothelial adhesion, is not required for extravasation from the peripheral knee vasculature. In contrast, almost no transmigration occurs in the absence of P66, an outer membrane protein that has porin and integrin adhesin functions. Importantly, P66 mutants specifically defective in integrin binding were incapable of promoting extravasation. P66 itself does not promote detectable microvascular interactions, suggesting that vascular adhesion of B. burgdorferi mediated by other adhesins, sets the stage for P66-integrin interactions leading to transmigration. Although integrin-binding proteins with diverse functions are encoded by a variety of bacterial pathogens, P66 is the first to have a documented and direct role in vascular transmigration. The emerging picture of vascular escape by the Lyme spirochete shows similarities, but distinct differences from leukocyte transmigration.

Author List

Kumar D, Ristow LC, Shi M, Mukherjee P, Caine JA, Lee WY, Kubes P, Coburn J, Chaconas G

Author

Jenifer Coburn PhD Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-84953273433   14 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Bacterial Proteins
Borrelia burgdorferi
Disease Models, Animal
Host-Pathogen Interactions
Intravital Microscopy
Lyme Disease
Mice
Mice, Inbred BALB C
Mice, Knockout
Microscopy, Confocal
Porins
Transendothelial and Transepithelial Migration
jenkins-FCD Prod-321 98992d628744e349846c2f62ac68f241d7e1ea70