Attenuation of MHC class II expression in macrophages infected with Mycobacterium bovis bacillus Calmette-Guerin involves class II transactivator anddepends on the Nramp1 gene
W. Wojciechowski et al., Attenuation of MHC class II expression in macrophages infected with Mycobacterium bovis bacillus Calmette-Guerin involves class II transactivator anddepends on the Nramp1 gene, J IMMUNOL, 163(5), 1999, pp. 2688-2696
The natural resistance associated macrophage protein 1 (Nramp1) gene determ
ines the ability of murine macrophages to control infection with a group of
intracellular pathogens, including Salmonella typhimurium, Leishmania dano
vani, and Mycobacterium bovis bacillus Calmette-Guerin (BCG). The expressio
n of the resistant allele of the Nramp1 gene in murine macrophages is assoc
iated with a more efficient expression of several macrophape activation-ass
ociated genes, including class II: MHC loci, In this study, we investigated
the molecular mechanisms involved in IFN-gamma-induced MHC class Il expres
sion in three types of macrophages: those expressing a wild-type allele of
the Nramp1 gene (B10R and 129/M phi), those carrying a susceptible farm of
the Namp1 gene (B10S), and those derived from 129-Nramp1-knockout mice (129
/Nramp1-KO). Previously, we published results showing that Ia protein expre
ssion is significantly higher in the IFN-gamma-induced B10R macrophages, co
mpared with its susceptible counterpart. In this paper, we also show that t
he higher expression of Ia protein in B10R cells is associated with higher
I-A(beta) mRNA expression, which correlates with a higher level of IFN-gamm
a-induced phosphorylation of the STAT1-alpha protein and subsequently with
elevated expression of class II transactivator (CIITA) mRNA, compared with
BIOS. Furthermore, we demonstrate that the infection of macrophages with M.
bovis BCG results in a down-regulation of CIITA mRNA expression and, conse
quently, in the inhibition of Ia induction. Therefore, our data explain, at
least in part, the: molecular mechanism involved in the inhibition of I-A(
beta) gene expression in M. bovis BCG-infected macrophages activated with I
FN-gamma.