Divergent outcomes following transcytosis of IgG targeting intracellular and extracellular chlamydial antigens.
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.
Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
Charles W
CW
Armitage
Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
Connor P
0000000220078126
CP
O'Meara
Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
Marina C G
MC
Harvie
Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
Peter
P
Timms
Division of Gastroenterology, Department of Medicine, Brigham & Women's Hospital, Harvard Digestive Diseases Centre, Harvard Medical School, Boston, MA, USA.
Richard S
RS
Blumberg
Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.
Kenneth W
KW
Beagley
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002690:Chlamydia Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D023502:Chlamydia muridarum / Q000276:immunology*; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000276:immunology; D005260:Female; D020868:Gene Silencing; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D042541:Intracellular Space / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D021381:Protein Transport; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism; D057900:Transcytosis / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; C100688:Fc receptor, neonatal