Details:

Alternative Title:
PLoS One
Publisher's site:
http://dx.doi.org/10.1371/journal.pone.0197413
Personal Author:
Williams, Shanna K. ; Weiner, Zachary P. ; Gilmore, Robert D.
Williams, Shanna K. ; Weiner, Zachary P. ; Gilmore, Robert D. Less -
Description:
Borrelia burgdorferi, the agent of Lyme borreliosis, can elude hosts' innate and adaptive immunity as part of the course of infection. The ability of B. burgdorferi to invade or be internalized by host cells in vitro has been proposed as a mechanism for the pathogen to evade immune responses or antimicrobials. We have previously shown that B. burgdorferi can be internalized by human neuroglial cells. In this study we demonstrate that these cells take up B. burgdorferi via coiling phagocytosis mediated by the formin, Daam1, a process similarly described for human macrophages. Following coincubation with glial cells, B. burgdorferi was enwrapped by Daam1-enriched coiling pseudopods. Coiling of B. burgdorferi was significantly reduced when neuroglial cells were pretreated with anti-Daam1 antibody indicating the requirement for Daam1 for borrelial phagocytosis. Confocal microscopy showed Daam1 colocalizing to the B. burgdorferi surface suggesting interaction with borrelial membrane protein(s). Using the yeast 2-hybrid system for identifying protein-protein binding, we found that the B. burgdorferi surface lipoprotein, BBA66, bound the FH2 subunit domain of Daam1. Recombinant proteins were used to validate binding by ELISA, pull-down, and co-immunoprecipitation. Evidence for native Daam1 and BBA66 interaction was suggested by colocalization of the proteins in the course of borrelial capture by the Daam1-enriched pseudopodia. Additionally, we found a striking reduction in coiling for a BBA66-deficient mutant strain compared to BBA66-expressing strains. These results show that coiling phagocytosis is a mechanism for borrelial internalization by neuroglial cells mediated by Daam1.
Subject:
[+]
Adaptive Immunity
Adaptor Proteins, Signal Transducing
Borrelia Burgdorferi
Brain Neoplasms
Cell Line, Tumor
Glioma
Humans
Immunity, Innate
Lipoproteins
Lyme Disease
Macrophages
Microfilament Proteins
Neuroglia
Neurons
Neutrophils
Phagocytosis
Protein Binding
Protein Domains
Recombinant Proteins
Rho GTP-Binding Proteins
Two-Hybrid System Techniques

Source:
PLoS One. 13(5).
Pubmed ID:
29746581
Pubmed Central ID:
PMC5944952
Document Type:
Journal Article
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:5908ac3e731da48e92ed89db6d32bc5679d18cc448ccca39e358de58225290f5
File Type:

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