Differential secretion of interleukin-12 (IL-12) subunits and heterodimeric IL-12p70 protein by CD-1 mice and murine macrophages in response to intracellular infection by Brucella abortus
L. Fernandez-lago et al., Differential secretion of interleukin-12 (IL-12) subunits and heterodimeric IL-12p70 protein by CD-1 mice and murine macrophages in response to intracellular infection by Brucella abortus, J MED MICRO, 48(12), 1999, pp. 1065-1073
The secretion of interleukin-12 (IL-12) following intracellular infection w
ith virulent Brucella abortus strain 2308 was investigated in CD-1 mice and
in CD-1 cultured peritoneal macrophages, Bioactive IL-12p70 and free non-i
mmunoactive p40 subunits (IL-12p40) were determined by enzyme-linked immuno
sorbent assays. In CD-1 mice, B. abortus 2308 was a potent inducer of IL-12
p40 (maximum levels mere 5.9 and 3.4 ng/ml in sera and spleen homogenates,
respectively). Secretion of IL-12p70 was also demonstrated in vivo, althoug
h at much lower levels (216.6 and 198.9 pg/ml in sera and spleen homogenate
s, respectively). Production of IL-12 over the first 7 days after infection
was accompanied by active multiplication of B. abortus in the spleens of i
nfected mice. CD-1 cultured peritoneal macrophages secreted only IL-12p40 (
878.4 pg/10(7) macrophages) in response to B. abortus infection and no prod
uction of IL-12p70 was observed. In contrast, CD-1 peritoneal macrophages s
ecreted detectable amounts of IL-12p70 (16.2 pg/10(7) macrophages) in respo
nse to purified lipopolysaccharide (S-LPS) from B, abortus 2308. The macrop
hages also secreted significant amounts of interferon-gamma (IFN-gamma) (52
0.1 pg/10(7) macrophages) in response to intracellular B. abortus, These re
sults indicate that B. abortus 2308 is not a potent inducer of IL-12p70 pro
duction, whereas purified S-LPS from B. abortus 2308 induces the secretion
of this bioactive form of IL-12 in cultured peritoneal macrophages. CD-1 pe
ritoneal macrophages were able to secrete IFN-gamma, as well as high amount
s of IL-12p40, in response to intracellular infection by B. abortus.