10.17863/CAM.427
Goh, Yun Shan
Armour, Kathryn L
Clark, Michael R
Grant, Andrew J
Mastroeni, Pietro
0000-0003-3838-4962
Igg Subclasses Targeting the Flagella of Salmonella enterica Serovar Typhimurium Can Mediate Phagocytosis and Bacterial Killing.
OMICS Publishing Group
2016
Antibody
Flagella
IgG subclasses
Opsonisation
Phagocytosis
Apollo - University of Cambridge Repository
University of Cambridge
013meh722
2016-06-24
2016-06-24
2016-05-30
eng
Article
https://www.repository.cam.ac.uk/handle/1810/256482
10.4172/2157-7560.1000322
Attribution 4.0 International
Attribution 4.0 International
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
http://creativecommons.org/licenses/by/4.0/
http://creativecommons.org/licenses/by/4.0/
open.access
Invasive non-typhoidal Salmonella are a common cause of invasive disease in immuno-compromised individuals and in children. Multi-drug resistance poses challenges to disease control, with a critical need for effective vaccines. Flagellin is an attractive vaccine candidate due to surface exposure and high epitope copy number, but its potential as a target for opsonophacytic antibodies is unclear. We examined the effect of targeting flagella with different classes of IgG on the interaction between Salmonella Typhimurium and a human phagocyte-like cell line, THP-1. We tagged the FliC flagellar protein with a foreign CD52 mimotope (TSSPSAD) and bacteria were opsonized with a panel of humanised CD52 antibodies with the same antigen-binding V-region, but different constant regions. We found that IgG binding to flagella increases bacterial phagocytosis and reduces viable intracellular bacterial numbers. Opsonisation with IgG3, followed by IgG1, IgG4, and IgG2, resulted in the highest level of bacterial uptake and in the highest reduction in the intracellular load of viable bacteria. Taken together, our data provide proof-of-principle evidence that targeting flagella with antibodies can increase the antibacterial function of host cells, with IgG3 being the most potent subclass. These data will assist the rational design of urgently needed, optimised vaccines against iNTS disease.
Biotechnology and Biological Sciences Research Council
BB/I002189/1
Medical Research Council
G1100102
Medical Research Council
G0001245
Medical Research Council
G0801161
Wellcome Trust
081743/Z/06/Z