Enhanced immunogenicity of theA19 Δmutant leads to accelerated clearance in the host.

Abstract

INTRODUCTION: is a Gram-negative facultative intracellular bacterium that can cause fever, abortion, and other symptoms in humans and various mammals., a type IV secretion system (T4SS) effector of, plays a critical role in regulatinginfection and inhibiting the host's innate immune response. METHODS: In this study, amutant strain ofA19 (Δ) was constructed using homologous recombination, and its biological characteristics, virulence, and immunogenicity were systematically investigated. RESULTS: The results showed that Δexhibited weakened resistance to in vitro stress, while its growth characteristics did not differ significantly from the wild-type strain A19. In the mouse immunization model, Δinduced weaker splenic pathological damage, and the splenic bacterial load was significantly lower than that of A19, indicating its reduced virulence. Additionally, Δinfection elicited stronger humoral and cellular immune responses in mice, including higher antibody levels, increased levels of Th1 cytokines (such as IFN-γ and IL-2), and enhanced proliferation and activity of CD8+ cells. Detection of Th1 and Th2 cells revealed that Δinduced stronger Th1 and Th2 responses in the spleen in the early stage, but the Th2 response weakened in the middle and late stages of infection. Notably, Δinfection did not suppress natural killer (NK) cell activity and even significantly enhanced its cytotoxic activity compared to the A19 strain. CONCLUSION: Our research demonstrates that Δleads to a reduced survival capacity of, while enhancing its immunogenicity. This suggestsis an important target for the prevention of.