Divergent outcomes following transcytosis of IgG targeting intracellular and extracellular chlamydial antigens

C W Armitage; C P O'Meara; M C Harvie; Peter Timms; R S Blumberg; K W Beagley

doi:10.1038/icb.2013.110

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Divergent outcomes following transcytosis of IgG targeting intracellular and extracellular chlamydial antigens

Journal article

Open access

Peer reviewed

Divergent outcomes following transcytosis of IgG targeting intracellular and extracellular chlamydial antigens

C W Armitage, C P O'Meara, M C Harvie, Peter Timms, R S Blumberg and K W Beagley

Immunology and Cell Biology, Vol.92(5), pp.417-426

2014

DOI: https://doi.org/10.1038/icb.2013.110

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Abstract

Immunology

Biochemistry and Cell Biology

IgG

Chlamydia

FcRn

vaccine

Antibodies can have a protective but non-essential role in natural chlamydial infections dependent on antigen specificity and antibody isotype. IgG is the dominant antibody in both male and female reproductive tract mucosal secretions, and is bi-directionally trafficked across epithelia by the neonatal Fc receptor (FcRn). Using pH-polarized epididymal epithelia grown on Transwells, IgG specifically targeted at an extracellular chlamydial antigen; the major outer membrane protein (MOMP), enhanced uptake and translocation of infection at pH 6-6.5 but not at neutral pH. This was dependent on FcRn expression. Conversely, FcRn-mediated transport of IgG targeting the intracellular chlamydial inclusion membrane protein A (IncA), induced aberrant inclusion morphology, recruited autophagic proteins independent of lysosomes and significantly reduced infection. Challenge of female mice with MOMP-specific IgG-opsonized Chlamydia muridarum delayed infection clearance but exacerbated oviduct occlusion. In male mice, MOMP-IgG elicited by immunization afforded no protection against testicular chlamydial infection, whereas the transcytosis of IncA-IgG significantly reduced testicular chlamydial burden. Together these data show that the protective and pathological effects of IgG are dependent on FcRn-mediated transport as well as the specificity of IgG for intracellular or extracellular antigens.

Details

Title: Divergent outcomes following transcytosis of IgG targeting intracellular and extracellular chlamydial antigens
Authors: C W Armitage (Author) - Queensland University of Technology
C P O'Meara (Author) - Queensland University of Technology
M C Harvie (Author) - Queensland University of Technology
Peter Timms (Author) - Queensland University of Technology
R S Blumberg (Author) - Harvard Medical School, United States
K W Beagley (Author) - Queensland University of Technology
Publication details: Immunology and Cell Biology, Vol.92(5), pp.417-426
Publisher: Nature Publishing Group
Date published: 2014
DOI: 10.1038/icb.2013.110
ISSN: 0818-9641
Copyright note: Copyright © 2014 Nature Publishing Group. The accepted version is reproduced here in accordance with the publishers copyright policy. The definitive version is available from http://www.nature.com/icb/
Organisation Unit: University of the Sunshine Coast, Queensland; Centre for Bioinnovation
Language: English
Record Identifier: 99448862302621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Cell Biology; Immunology

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