Treatment of Brucella-susceptible mice with IL-12 increases primary and secondary immunity.
Brucella spp. cause disease in humans and livestock and are potential biowarfare agents. Defining the protective immune response is necessary to design vaccines. This has largely been done with mice, brucella-susceptible BALB/c and resistant C57BL strains. Since interferon-gamma is key to brucella resistance, contrary to expectations, we found that ex vivo splenocytes from naïve BALB/c mice produced IL-12 and interferon-gamma in cultures with brucellae at levels comparable to those of splenocytes from the more resistant C57BL/10 mice. Moreover, both IL-12 and interferon-gamma were produced in the first week following infection of BALB/c mice. However, by the third week of infection we found decreased IL-12Rbeta2 expression by BABL/c splenocytes, corresponding to their inability to produce interferon-gamma in Brucella recall responses at this time as reported previously. Administering recombinant IL-12 to these mice ameliorated the interferon-gamma hiatus, resulted in a 1000-fold reduction in CFU during primary infection and increased survival following secondary challenge.
Sathiyaseelan
Janaki
J
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Goenka
Radhika
R
Parent
Michelle
M
Benson
Rita M
RM
Murphy
Erin A
EA
Fernandes
Dancella M
DM
Foulkes
Andrea S
AS
Baldwin
Cynthia L
CL
D000818:Animals; D002003:Brucella abortus / Q000276:immunology*; D002006:Brucellosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D004198:Disease Susceptibility; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053707:Receptors, Interleukin-12 / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*
C508443:Il12rb2 protein, mouse; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D007371:Interferon-gamma