Attenuated Yersinia enterocolitica mutant strains exhibit differential virulence in cytokine-deficient mice: implications for the development of novel live carrier vaccines
التفاصيل البيبلوغرافية
العنوان:
Attenuated Yersinia enterocolitica mutant strains exhibit differential virulence in cytokine-deficient mice: implications for the development of novel live carrier vaccines
Yersiniaenterocoliticamutant strains, including mutants deficient in the chaperone SycH resulting in a functional deficiency in tyrosine phosphatase (YopH), Mn-cofactored superoxide dismutase (SodA), iron-repressive protein 1 (IRP-1), andYersiniaadhesin A (YadA), were demonstrated to be highly attenuated in wild-type C57BL/6 mice. TNFRp55−/−, IL-12p40−/−, and IL-18−/−mutant mice, in which theYersiniawild-type strain causes severe systemic infections, were used to investigate whether theseYersiniamutant strains would be attenuated in immunodeficient hosts. A plasmid-curedYersiniamutant strain was unable to colonize any of the mutant mice tested. A SycH-deficient mutant strain colonized intestinal tissues of these mice but was attenuated for systemic infection in all of the mutant mice. Both YadA- and Irp-1-deficientYersiniamutants were still attenuated in IL-12−/−and IL-18−/−mice but were pathogenic in TNFRp55−/−mice. By contrast, aYersiniasodAmutant was highly pathogenic for TNFRp55−/−and IL-12p40−/−mice while interleukin-18 (IL-18) was dispensable. This finding demonstrates that certain virulence factors enable yersiniae to compete with distinct cytokine-dependent host defense mechanisms. Moreover, while gamma interferon mRNA expression did not reflect protective host responses in cytokine-deficient mice, IL-10 expression coincided with a heavy splenic bacterial load and was associated with progressive infection courses. We can thus segregate minor (SodA), intermediate (YadA and IRP-1), and major (YopH) virulence factors ofY.enterocolitica. Finally, we demonstrate that, even in immunocompromised hosts,YersiniasycHand, with some restrictions,irp-1mutants may be suitable for use as live carrier vaccines.
