Gene expression in IFN-gamma-activated murine macrophages

Abstract

Macrophages are critical for natural immunity and play a central role in specific acquired immunity. The IFN-γ activation of macrophages derived from A/J or BALB/c mice yielded two different patterns of antiviral state in murine hepatitis virus 3 infection, which were related to a down-regulation of the main virus receptor. Using cDNA hybridization to evaluate mRNA accumulation in the cells, we were able to identify several genes that are differently up-or down-regulated by IFN-γ in A/J (267 and 266 genes, respectively, up-and down-regulated) or BALB/c (297 and 58 genes, respectively, up-and downregulated) mouse macrophages. Macrophages from mice with different genetic backgrounds behave differently at the molecular level and comparison of the patterns of non-activated and IFN-γ-activated A/J or BALB/c mouse macrophages revealed, for instance, an up-regulation and a down-regulation of genes coding for biological functions such as enzymatic reactions, nucleic acid synthesis and transport, protein synthesis, transport and metabolism, cytoskeleton arrangement and extracellular matrix, phagocytosis, resistance and susceptibility to infection and tumors, inflammation, and cell differentiation or activation. The present data are reported in order to facilitate future correlation of proteomic/transcriptomic findings as well as of results obtained from a classical approach for the understanding of biological phenomena. The possible implication of the role of some of the gene products relevant to macrophage biology can now be further scrutinized. In this respect, a down-regulation of the main murine hepatitis virus 3 receptor gene was detected only in IFN-γ-activated macrophages of resistant mice.

Mouse Hepatitis Virus 3 Binding to Macrophages Correlates with Resistance to Experimental Infection

“…Only resistant A/J macrophages show a decreased expression of the gene encoding for the principal viral receptor (Bgp 1a ) [3]. Our quantitative biology studies [1, 4] showing upregulated and downregulated proteins and genes in resistant and susceptible macrophages opened a great perspective for investigations of the biological role of these cells and have also confirmed the downregulation of an MHV3 receptor gene by IFN‐γ activation [4].…”

“…These proteomic studies – done years before the term ‘proteomics’ was invented – represented a turning point in my approach to understanding the basis of anti‐MHV state induced by IFN‐γ. A few years later, supported by the Swiss National Science Foundation, we have found that IFN‐γ was capable of inducing a downregulation of the main viral receptor only in macrophages originated from resistant mice, explaining at least in part the cellular and molecular basis of mouse resistance to MHV infection [3, 4].…”

The Road Less Traveled: SARS-CoV-2 and Cell-Mediated Immunity

“…Notably, INF-g has been found to downregulate expression of ACE2 (the receptor for SARS-CoV-2), 5 and this downregulation in macrophages is correlated with the latter becoming refractory to infection with the closely related coronavirus MHV3. 6 Collectively, these noteworthy studies suggest that perhaps we may have largely focused on the wrong arm of the immune response. These insights bode well for those vaccines, such as mRNA or DNA vaccines, that express viral proteins from within the context of a cell to induce a cell-mediated response.…”