IL-10 Overexpression Reduces the Protective Response of an Experimental Chlamydia abortus Vaccine in a Murine Model.

Simple Summary: Chlamydia abortus causes intracellular persistent infections in sheep, requiring a strong immune response for resolution. Interleukin-10 (IL-10) plays a dual role by modulating the inflammatory immune response during infection and preventing damage during pregnancy. This study used transgenic mice overexpressing IL-10 to model chronic C. abortus infections. The goal was to test the effectiveness of an experimental vaccine and understand the immune mechanisms involved when high levels of IL-10 are present. Both transgenic and control mice were vaccinated and exposed to the bacteria. Results showed that vaccinated control mice cleared the infection by day 9, while transgenic mice still had bacteria at day 28. Vaccination increased a key immune response, with IFN-γ and iNOS production, but did not change IL-10 levels in transgenic mice. Additionally, fewer immune cells were recruited in vaccinated transgenic mice. The study concludes that vaccine effectiveness is reduced in presence of high IL-10 levels. This model could be used for the development of better vaccines against C. abortus, and could help to test vaccines requiring strong cellular immune responses, thereby benefiting animal health. In ovine populations, the enzootic nature of Chlamydia abortus (C. abortus) is attributed to its capacity to establish persistent intracellular infections, which necessitate a cellular immune response mediated by interferon-gamma (IFN-γ) for effective resolution. In both natural hosts and murine models, interleukin-10 (IL-10) has been demonstrated to modulate the cellular immune response crucial for the eradication of C. abortus. During gestation, it has also been shown to play a role in preventing inflammatory damage to gestational tissues and foetal loss through the downregulation of pro-inflammatory cytokines. This paradigm can be key for events leading to a protective response towards an infectious abortion. Previous research successfully established a mouse model of chronic C. abortus infection using transgenic mice overexpressing IL-10 (IL-10tg), simulating the dynamics of chronic infection observed in non-pregnant natural host. This study aims to evaluate the efficacy of an experimental inactivated vaccine against C. abortus and to elucidate the immune mechanisms involved in protection during chronic infection using this model. Transgenic and wild-type (WT) control mice were immunized and subsequently challenged with C. abortus. Vaccine effectiveness and immune response were assessed via immunohistochemistry and cytokine serum levels over a 28-day period. Morbidity, measured by daily weight loss, was more pronounced in non-vaccinated transgenic IL-10 mice, though no mortality was observed in any group. Vaccinated control mice eliminated the bacterial infection by day 9 post-infection (p.i.), whereas presence of bacteria was noted in vaccinated transgenic IL-10 mice until day 28 p.i. Vaccination induced an early post-infection increase in IFN-γ production, but did not alter IL-10 production in transgenic mice. Histological analysis indicated suboptimal recruitment of inflammatory cells in vaccinated transgenic IL-10 mice compared to WT controls. In summary, the findings suggest that IL-10 overexpression in transgenic mice diminishes the protective efficacy of vaccination, confirming that this model can be useful for validating the efficacy of vaccines against intracellular pathogens such as C. abortus that require robust cell-mediated immunity. [ABSTRACT FROM AUTHOR]