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

• Published in: Animals (Basel) Vol. 14; no. 16; p. 2322
• Main Authors: Del Río, Laura, Salinas, Jesús, Ortega, Nieves, Buendía, Antonio J, Navarro, Jose A, Caro, María Rosa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.08.2024; MDPI
• Subjects: Abortion; Antigen presentation; BCG; BCG vaccines; C. abortus; Chlamydia; chronic infection; Cytokines; Health aspects; IL-10; Immunology; Infection; Infections; Liver; Livestock; macIL-10 transgenic mice; Medical research; Medicine, Experimental; Morbidity; mouse model; Pathogens; Pregnant women; Sheep; Transgenic animals; Tumor necrosis factor-TNF; vaccine; Vaccines; Spain; United States > US; vaccine; C. abortus; mouse model; chronic infection; macIL-10 transgenic mice; IL-10
• ISSN: 2076-2615; 2076-2615
• DOI: 10.3390/ani14162322

In ovine populations, the enzootic nature of ( ) is attributed to its capacity to establish persistent intracellular infections, which necessitate a cellular immune response mediated by interferon-gamma (IFN- ) 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 . 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 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 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 . 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- 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 that require robust cell-mediated immunity.