ABSTRACT
Macrophages are critical for natural immunity and play a central role in specific acquired immunity. The IFN-gamma 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-gamma in A/J (267 and 266 genes, respectively, up- and down-regulated) or BALB/c (297 and 58 genes, respectively, up- and down-regulated) 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-gamma-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-gamma-activated macrophages of resistant mice.
Subject(s)
Animals , Gene Expression Regulation, Viral/genetics , Interferon-gamma/pharmacology , Macrophage Activation/genetics , Macrophages/virology , Murine hepatitis virus/genetics , Cells, Cultured , Gene Expression Regulation, Viral/immunology , Mice , Mice, Inbred A , Mice, Inbred BALB C , Macrophage Activation/immunology , Macrophages/drug effects , Macrophages/immunology , Murine hepatitis virus/immunology , Murine hepatitis virus/physiology , RNA, Messenger , Virus ReplicationABSTRACT
We studied 88 multibacillary (MB) leprosy patients, who received multidrug therapy (MDT) treatment in hyperendemic (44 persons) and hypoendemic (44 persons) areas in Gowa Regency, South Sulawesi, Indonesia. Bacteriological examinations were carried out (bacteria index and morphology index), immunological examinations (MLPA and TNF-alpha) and genetic variation in blood and ear lobe slit skin smears of MB leprosy patients, which had been treated by MDT, were performed. The collected data were analyzed with the chi-square test and discriminant analysis. Eight persons (9.1%) had a positive bacteria index and 2 persons (2.4%) had a morphology index. All patients (100%) increased their TNF-alpha concentration. All the samples (100%) showed an increase in the TNF-alpha concentration, compared to controls. MLPA positive conversion was found in 4 persons (47.7% samples) and TNF-alpha gene genetic variation at the position of -308, occurred in 12 persons (13.6% samples). Statistic test results showed a significant difference (p<0.01) in the TNF-alpha concentration between hyperendemic and hypoendemic areas. On the basis of a positive conversion by bacteriological results and its association with immunological results, it can be concluded that multibacillary leprosy patients with MDT treatment did not become a source of leprosy transmission.