In:
eLife, eLife Sciences Publications, Ltd, Vol. 4 ( 2015-12-09)
Abstract:
The outer surfaces of animal cells are coated with proteins, including many that are able to sense signals from the environment. The integrins are one such group of proteins. Particular ions or small molecules – collectively known as ligands – can bind to these proteins and activate cascades of signaling events inside the cell. An integrin called complement receptor 3 (CR3) resides on the surface of many immune cells. CR3 binds to molecules found on the surface of bacteria, and prompts the immune cell to engulf and destroy the bacteria. The ligands bind to a region of CR3 called the I-domain, and it is thought that this domain is only able to accept ligands once the integrin protein has adopted an active form. Bordetella pertussis – the bacterium that causes a disease called whooping cough – subverts the immune defenses of the host. B. pertussis produces a toxin known as adenylate cyclase toxin (CyaA) that binds to CR3 in order to penetrate the immune cell and stop immune responses from being activated. However, it is not clear how CyaA is able to bind to CR3 without activating the signaling cascades. Here, Osicka et al. used biochemical techniques to address this question. The experiments reveal that CyaA mostly binds to an inactive form of CR3 through a unique site outside of the I-domain. It enables the toxin to use the integrin without triggering an immune response. Furthermore, the experiments show how CyaA prevents ligand signaling via CR3 proteins to allow B. pertussis to shut down the host’s first line of defense against infection. Osicka et al.’s findings show how CyaA evades the host’s immune system and highlight the central role played by this toxin in B. pertussis infections. In the future, these findings could inform efforts to produce more effective vaccines against whooping cough.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.10766.001
DOI:
10.7554/eLife.10766.002
DOI:
10.7554/eLife.10766.003
DOI:
10.7554/eLife.10766.004
DOI:
10.7554/eLife.10766.005
DOI:
10.7554/eLife.10766.006
DOI:
10.7554/eLife.10766.007
DOI:
10.7554/eLife.10766.008
DOI:
10.7554/eLife.10766.009
DOI:
10.7554/eLife.10766.010
DOI:
10.7554/eLife.10766.011
DOI:
10.7554/eLife.10766.012
DOI:
10.7554/eLife.10766.013
DOI:
10.7554/eLife.10766.014
DOI:
10.7554/eLife.10766.015
DOI:
10.7554/eLife.10766.016
DOI:
10.7554/eLife.10766.017
DOI:
10.7554/eLife.10766.018
DOI:
10.7554/eLife.10766.019
DOI:
10.7554/eLife.10766.020
DOI:
10.7554/eLife.10766.021
DOI:
10.7554/eLife.10766.022
DOI:
10.7554/eLife.10766.023
DOI:
10.7554/eLife.10766.024
DOI:
10.7554/eLife.10766.025
DOI:
10.7554/eLife.10766.026
DOI:
10.7554/eLife.10766.027
DOI:
10.7554/eLife.10766.028
DOI:
10.7554/eLife.10766.029
DOI:
10.7554/eLife.10766.030
DOI:
10.7554/eLife.10766.031
DOI:
10.7554/eLife.10766.032
DOI:
10.7554/eLife.10766.033
DOI:
10.7554/eLife.10766.034
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2015
detail.hit.zdb_id:
2687154-3
Permalink