OPPOSING EFFECTS OF INTERFERON-GAMMA ON INOS AND INTERLEUKIN-10 EXPRESSION IN LIPOPOLYSACCHARIDE-STIMULATED AND MYCOBACTERIAL LIPOARABINOMANNAN-STIMULATED MACROPHAGES
Tia. Roach et al., OPPOSING EFFECTS OF INTERFERON-GAMMA ON INOS AND INTERLEUKIN-10 EXPRESSION IN LIPOPOLYSACCHARIDE-STIMULATED AND MYCOBACTERIAL LIPOARABINOMANNAN-STIMULATED MACROPHAGES, Immunology, 85(1), 1995, pp. 106-113
Previous studies have demonstrated that, like bacterial lipopolysaccha
ride (LPS), arabinofuranosyl-terminated lipoarabinomannan (AraLAM) fro
m an attenuated strain of Mycobacterium induces potent early gene (c-f
os, KC, JE and TNF-alpha) responses in murine macrophages, whereas ext
ensively alpha-Manp capped LAM (ManLAM) from virulent M. tuberculosis
do not. In this study we have extended analysis of the influence of my
cobacterial LAM on macrophage function by demonstrating that AraLAM. (
but not ManLAM), like bacterial LPS, is a potent stimulator of inducib
le nitric oxide synthase (iNOS) expression independent of the autocrin
e activity of co-stimulated tumour necrosis factor-alpha (TNF-alpha) r
elease. The inability of ManLAM to induce iNOS expression was not due
to induction of the 'deactivating' cytokine interleukin-10 (IL-10). In
deed, like LPS, AraLAM was also a potent inducer of IL-10 expression.
However, analysis of AraLAM- or LPS-induced responses in the presence
of interferon-gamma (IFN-gamma) showed that, whereas IFN-gamma, acts a
s a potent co-stimulus for iNOS, it completely inhibits the IL-10 resp
onse. Hence, the presence of IFN-gamma early in infection, will have a
n important immunomodulatory role in determining the macrophage respon
se. These results have important implications for the pathogenesis of
virulent and avirulent mycobacteria in vivo.