Adhesion molecules and effector T cells subsets associated with female genital tract infection
[eng] Common sexually transmitted infections like gonorrhea, Chlamydia, syphilis, and trichomoniasis are the leading cause of morbidity in developing countries. Adolescents and young women have the highest rates of STIs in developing countries. Pre-existing female genital tract infections affect the...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/207158 |
| Acceso en línea: | https://hdl.handle.net/2445/207158 http://hdl.handle.net/10803/689971 |
| Access Level: | acceso abierto |
| Palabra clave: | Uroginecologia Malalties de transmissió sexual Cèl·lules T Immunologia Infeccions Urogynecology Sexually transmitted diseases T cells Immunology Infections |
| Sumario: | [eng] Common sexually transmitted infections like gonorrhea, Chlamydia, syphilis, and trichomoniasis are the leading cause of morbidity in developing countries. Adolescents and young women have the highest rates of STIs in developing countries. Pre-existing female genital tract infections affect the development and pathogenesis of other sexually transmitted infections, leading to long-term consequences such as pelvic inflammatory disease, cancer, and infertility. Efforts to develop vaccines against sexually transmitted infections have been hindered by the inability to measure immune responses in the genital tract. Effective vaccines should generate localized immune responses at potential exposure sites to provide faster and more robust infection control. Assays rely on blood samples to provide a complete picture of cellular traffic between lymph nodes and the mucosa, especially soon after infection. Studying and characterizing the homing profile of T cells becomes crucial to understanding mucosal immune responses against infections, and new methods to measure and manipulate immune responses are needed to develop effective STI vaccines. In this study, we examined how adhesion molecules are expressed by circulating effector T cells following mucosal infection of the female genital tract in mice and during symptomatic episodes of vaginosis in women. In a mouse model of Chlamydia infection, we observed preferential expression of CCR2, CCR5, CXCR6, and CD11c. However, during bacterial vaginosis in women, only CCR5 and CD11c were prominently expressed by effector T cells. We also investigated other homing molecules, like α4β1 and α4β7, previously suggested as essential for homing to the genital mucosa. Interestingly, these molecules showed differential expression in the patients. Surprisingly, CD11c, an integrin chain not commonly analyzed in the context of T cell immunity, was consistently elevated in all activated effector CD8+ T cell subsets studied. Additionally, CD11c expression was induced after systemic infection in mice, indicating that it is not exclusive to genital tract infection. Microarray analyses of activated effector T cells expressing CD11c from naïve mice revealed enrichment for genes associated with natural killer cells. Notably, flow cytometry analysis of murine CD11c+ T cells showed markers typically linked with non-conventional T cell subsets, such as γδ T cells and invariant natural killer T cells. However, in women, the CD11c fraction of blood and cervical tissue mainly consisted of γδ T cells and CD8+ T cells. These CD11c+ cells exhibited high activation levels and greater interferon (IFN)-γ secretion compared to CD11c- T cells. Moreover, circulating CD11c+ T cells in women correlated with the expression of multiple adhesion molecules, indicating a high potential for tissue homing. Our findings suggest that CD11c expression distinguishes a specific population of circulating T cells during bacterial infection, displaying innate capacity and mucosal homing potential. Furthermore, its increase in response to genital tract disorders may serve as a novel surrogate marker of mucosal immunity in women, offering potential applications in diagnostics and therapeutics. Further investigation is warranted to explore this potential thoroughly. |
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