IgG exacerbates genital chlamydial pathology in females by enhancing pathogenic CD8<sup>+</sup> T cell responses

Armitage, CW; O'Meara, CP; Bryan, ER; Kollipara, A; Trim, LK; Hickey, D; Carey, AJ; Huston, WM; Donnelly, G; Yazdani, A; Blumberg, RS; Beagley, KW

IgG exacerbates genital chlamydial pathology in females by enhancing pathogenic CD8<sup>+</sup> T cell responses

Armitage, CW O'Meara, CP Bryan, ER Kollipara, A Trim, LK Hickey, D Carey, AJ Huston, WM Donnelly, G Yazdani, A Blumberg, RS Beagley, KW

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Publisher:: WILEY
Publication Type:: Journal Article
Citation:: Scandinavian Journal of Immunology, 2023
Issue Date:: 2023-01-01

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Field	Value	Language
dc.contributor.author	Armitage, CW
dc.contributor.author	O'Meara, CP
dc.contributor.author	Bryan, ER
dc.contributor.author	Kollipara, A
dc.contributor.author	Trim, LK
dc.contributor.author	Hickey, D
dc.contributor.author	Carey, AJ
dc.contributor.author	Huston, WM
dc.contributor.author	Donnelly, G
dc.contributor.author	Yazdani, A
dc.contributor.author	Blumberg, RS
dc.contributor.author	Beagley, KW
dc.date.accessioned	2023-12-08T06:05:59Z
dc.date.available	2023-12-08T06:05:59Z
dc.date.issued	2023-01-01
dc.identifier.citation	Scandinavian Journal of Immunology, 2023
dc.identifier.issn	0300-9475
dc.identifier.issn	1365-3083
dc.identifier.uri	http://hdl.handle.net/10453/173776
dc.description.abstract	Chlamydia trachomatis infections are an important sexually transmitted infection that can lead to inflammation, scarring and hydrosalpinx/infertility. However, infections are commonly clinically asymptomatic and do not receive treatment. The underlying cause of asymptomatic immunopathology remains unknown. Here, we demonstrate that IgG produced during male infection enhanced the incidence of immunopathology and infertility in females. Human endocervical cells expressing the neonatal Fc Receptor (FcRn) increased translocation of human IgG-opsonized C. trachomatis. Using total IgG purified from infected male mice, we opsonized C. muridarum and then infected female mice, mimicking sexual transmission. Following infection, IgG-opsonized Chlamydia was found to transcytose the epithelial barrier in the uterus, where it was phagocytosed by antigen-presenting cells (APCs) and trafficked to the draining lymph nodes. APCs then expanded both CD4+ and CD8+ T cell populations and caused significantly more infertility in female mice infected with non-opsonized Chlamydia. Enhanced phagocytosis of IgG-opsonized Chlamydia significantly increased pro-inflammatory signalling and T cell proliferation. As IgG is transcytosed by FcRn, we utilized FcRn−/− mice and observed that shedding kinetics of Chlamydia were only affected in FcRn−/− mice infected with IgG-opsonized Chlamydia. Depletion of CD8+ T cells in FcRn−/− mice lead to a significant reduction in the incidence of infertility. Taken together, these data demonstrate that IgG seroconversion during male infection can amplify female immunopathology, dependent on FcRn transcytosis, APC differentiation and enhanced CD8 T cell responses.
dc.language	English
dc.publisher	WILEY
dc.relation.ispartof	Scandinavian Journal of Immunology
dc.relation.isbasedon	10.1111/sji.13331
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology
dc.subject.classification	Immunology
dc.subject.classification	3204 Immunology
dc.title	IgG exacerbates genital chlamydial pathology in females by enhancing pathogenic CD8<sup>+</sup> T cell responses
dc.type	Journal Article
utslib.for	1107 Immunology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	open_access	*
dc.date.updated	2023-12-08T06:05:57Z
pubs.publication-status	Published

Abstract:

Chlamydia trachomatis infections are an important sexually transmitted infection that can lead to inflammation, scarring and hydrosalpinx/infertility. However, infections are commonly clinically asymptomatic and do not receive treatment. The underlying cause of asymptomatic immunopathology remains unknown. Here, we demonstrate that IgG produced during male infection enhanced the incidence of immunopathology and infertility in females. Human endocervical cells expressing the neonatal Fc Receptor (FcRn) increased translocation of human IgG-opsonized C. trachomatis. Using total IgG purified from infected male mice, we opsonized C. muridarum and then infected female mice, mimicking sexual transmission. Following infection, IgG-opsonized Chlamydia was found to transcytose the epithelial barrier in the uterus, where it was phagocytosed by antigen-presenting cells (APCs) and trafficked to the draining lymph nodes. APCs then expanded both CD4+ and CD8+ T cell populations and caused significantly more infertility in female mice infected with non-opsonized Chlamydia. Enhanced phagocytosis of IgG-opsonized Chlamydia significantly increased pro-inflammatory signalling and T cell proliferation. As IgG is transcytosed by FcRn, we utilized FcRn−/− mice and observed that shedding kinetics of Chlamydia were only affected in FcRn−/− mice infected with IgG-opsonized Chlamydia. Depletion of CD8+ T cells in FcRn−/− mice lead to a significant reduction in the incidence of infertility. Taken together, these data demonstrate that IgG seroconversion during male infection can amplify female immunopathology, dependent on FcRn transcytosis, APC differentiation and enhanced CD8 T cell responses.

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http://hdl.handle.net/10453/173776