Other authors have recently demonstrated that L. amazonensis is able to induce a transcriptional signature
that resembles deactivation yet also appears similar to an alternative macrophage activation signature [22]. Interestingly, these authors showed that L. amazonensis Caspase-dependent apoptosis directs macrophage response towards lipid and polyamine pathways by activating parasite- and host tissue-protective processes [22]. The role that host genetic Selleck HDAC inhibitor factors play in the outcome of pathogen infection has also been studied using microarray analysis [23, 24]. In addition, several studies have compared the gene expression profiles of cells [23, 24] and tissues [25] from a variety of mouse strains in response to several pathogens. However, no studies have yet attempted to compare the transcriptional signatures of uninfected macrophages from two distinct murine genetic backgrounds, nor the transcriptional programs of a distinct macrophage Wnt inhibitor review lineage in response to a single Leishmania species. The present study employed a transcriptomic approach combined with biological network
analysis to highlight the differences between the responses of murine macrophages from two inbred mouse strains to L. amazonensis infection. C57BL/6 and CBA strains were selected due to their divergent degrees of susceptibility to this parasite [4, 12]. The expression profiles of more than 12,000 murine genes were evaluated in each mouse strain before and after infection in vitro. The authors identified the genes that were differentially expressed between uninfected
C57BL/6 and CBA macrophages, thereby establishing baseline Phosphoglycerate kinase levels of differential expression. We then attempted to investigate modulations in macrophage gene expression, before and after infection, within a given mouse strain. We showed that the transcriptional profile of uninfected C57BL/6 macrophages differed from that of CBA macrophages with respect to the modulation of genes involved in the macrophage pathway of activation. In response to infection, C57BL/6 macrophages up-regulate genes related to controlling infection, while CBA cells up-regulate genes involved in lipid metabolism. These findings provide evidence that C57BL/6 macrophages’ transcriptional profiles may help in the control of L. amazonensis infection, in contrast to the profiles of CBA cells. Methods Mice All experiments were performed according to the guidelines of the Institutional Review Board on Animal Experimentation at the Oswaldo Cruz Foundation – CPqGM/FIOCRUZ. Male and female CBA mice, 6-12 weeks old, were provided by the Animal Care Facility at CPqGM/FIOCRUZ. The animals were housed under specific pathogen-free conditions, fed commercial rations and given water ad libitum. Parasites The L.