Induction of innate immunity by IL-2-expressing Salmonella confers protection against lethal infection.
Previously, we demonstrated that an attenuated Salmonella strain expressing IL-2 (designated GIDIL2) is cleared from the circulation at a much faster rate than the non-cytokine-expressing parental strain (designated BRD509). These findings suggested that IL-2 expression led to the rapid induction of innate immune responses that, in turn, accounted for the accelerated rate of bacterial clearance. In the present study, the mechanism by which this early antibacterial response is mediated was investigated. We demonstrate that as early as 2 h after infection with GIDIL2, but not BRD509, peritoneal excudate cells exhibited enhanced NK cytotoxic activity and upregulated NOS2 mRNA and NO production. This early response coincided with an enhancement of GIDIL2 clearance from the peritoneal cavity, first evidenced 22 h post-infection. Moreover, it conferred a high level of protection against virulent Salmonella challenge given within 16-20 h of GIDIL2 administration. These findings highlight the importance of innate immunity in the control of early bacterial proliferation and demonstrate the rapidity by which these responses are induced following bacterial entry.
al-Ramadi
Basel K
BK
Department of Medical Microbiology, Faculty of Medicine and Health Sciences, UAE University, PO Box 17666, Al Ain, United Arab Emirates. ramadi.b@uaeu.ac.ae
Mustafa
Nada
N
AbouHaidar
Mounir
M
Fernandez-Cabezudo
Maria J
MJ
D000818:Animals; D015169:Colony Count, Microbial; D003602:Cytotoxicity, Immunologic; D005260:Female; D015870:Gene Expression; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics; D012475:Salmonella / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D014774:Virulence / Q000276:immunology
D007376:Interleukin-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse