Poor survival but high immunogenicity of IL-2-expressing Salmonella typhimurium in inherently resistant mice.
An IL-2-expressing, attenuated strain of Salmonella typhimurium (strain GIDIL2) was previously shown to survive poorly and to have lower immunogenicity in susceptible mice than its parental, non-cytokine-expressing strain (designated BRD509). In the present study, we compared the immune responses induced by both bacterial strains in inherently Salmonella-resistant C3H/HeN mice. Analysis of the bacterial loads in the peritoneum and spleen revealed that colony-forming units (CFUs) of GIDIL2 were consistently lower than the corresponding BRD509 CFUs. As early as 48 h after inoculation, there were 60-fold lower CFUs of GIDIL2 than BRD509 organisms in the peritoneal cavity. Similarly, the differences in splenic CFUs of GIDIL2 were 20- to 50-fold lower than those of BRD509 over a period of 3-21 days post-injection. This rapid rate of clearance of the GIDIL2 organisms correlated with significantly decreased infection-induced splenomegaly and nitric oxide production by spleen cells. However, despite the poor survival of GIDIL2 organisms in vivo, they could activate peritoneal NK cells efficiently. As early as 48 h after immunization, equivalent levels of NK-mediated cellular cytotoxicity were induced by BRD509 and GIDIL2 strains. Direct evidence for priming of the immune response was shown by demonstrating increased production of IFN-gamma in a recall response by spleen memory T cells obtained 3 weeks after immunization. Finally, mice inoculated with a single dose of either BRD509 or GIDIL2 organisms were fully protected against a challenge of >100-fold the LD50 dose of virulent Salmonella. Taken together, our data demonstrate that despite their rapid clearance from the reticuloendothelial system, IL-2-expressing Salmonella are immunogenic and fully capable of affording excellent protection against virulent challenge in Salmonella-resistant C3H/HeN mice.
al-Ramadi
Basel K
BK
Department of Medical Microbiology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE. ramadi.b@uaeu.ac.ae
Bashir
Ghada
G
Rizvi
Tahir A
TA
Fernandez-Cabezudo
Maria J
MJ
D000818:Animals; D015169:Colony Count, Microbial; D007113:Immunity, Innate; D007114:Immunization; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D010537:Peritoneum / Q000276:immunology / Q000382:microbiology; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000401:mortality* / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D013154:Spleen / Q000276:immunology / Q000382:microbiology
D007376:Interleukin-2