title: Differential transcriptional response in macrophages infected with cell wall deficient versus normal Mycobacterium Tuberculosis.
abstract: Host-pathogen interactions determine the outcome following infection by mycobacterium tuberculosis (Mtb). Under adverse circumstances, normal Mtb can form cell-wall deficient (CWD) variants within macrophages, which have been considered an adaptive strategy for facilitating bacterial survival inside macrophages. However, the molecular mechanism by which infection of macrophages with different phenotypic Mtb elicits distinct responses of macrophages is not fully understood. To explore the molecular events triggered upon Mtb infection of macrophages, differential transcriptional responses of RAW264.7 cells infected with two forms of Mtb, CWD-Mtb and normal Mtb, were studied by microarray analysis. Some of the differentially regulated genes were confirmed by RT-qPCR in both RAW264.7 cells and primary macrophages. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was used to analyze functions of differentially expressed genes. Distinct gene expression patterns were observed between CWD-Mtb and normal Mtb group. Mapt was up-regulated, while NOS2 and IL-11 were down-regulated in CWD-Mtb infected RAW264.7 cells and primary macrophages compared with normal Mtb infected ones. Many deregulated genes were found to be related to macrophages activation, immune response, phagosome maturation, autophagy and lipid metabolism. KEGG analysis showed that the differentially expressed genes were mainly involved in MAPK signaling pathway, nitrogen metabolism, cytokine-cytokine receptor interaction and focal adhesion. Taken together, the present study showed that differential macrophage responses were induced by intracellular CWD-Mtb an normal Mtb infection, which suggested that interactions between macrophages and different phenotypic Mtb are very complex. The results provide evidence for further understanding of pathogenesis of CWD-Mtb and may help in improving strategies to eliminate intracellular CWD-Mtb.
authors.affiliation: 1. Department of Laboratory Medicine of Affiliated Hospital of Weifang Medical University, Key Laboratory of Clinical Laboratory Diagnostics in Universities of Shandong and Medical Priority Speciality of Clinical Laboratory in Shandong Province, Weifang Medical University, Weifang 261031, China; ; 2. Department of Medical Microbiology, Weifang Medical University, Weifang 261053, China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Fu
authors.affiliation: 1. Department of Laboratory Medicine of Affiliated Hospital of Weifang Medical University, Key Laboratory of Clinical Laboratory Diagnostics in Universities of Shandong and Medical Priority Speciality of Clinical Laboratory in Shandong Province, Weifang Medical University, Weifang 261031, China;
authors.forename: Kun-Shan
authors.initials: KS
authors.lastname: Gao
authors.affiliation: 2. Department of Medical Microbiology, Weifang Medical University, Weifang 261053, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ji
authors.affiliation: 1. Department of Laboratory Medicine of Affiliated Hospital of Weifang Medical University, Key Laboratory of Clinical Laboratory Diagnostics in Universities of Shandong and Medical Priority Speciality of Clinical Laboratory in Shandong Province, Weifang Medical University, Weifang 261031, China;
authors.forename: Zheng-Jun
authors.initials: ZJ
authors.lastname: Yi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002473:Cell Wall / Q000473:pathology*; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology*; D051379:Mice; D046228:Microarray Analysis; D009169:Mycobacterium tuberculosis / Q000166:cytology* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology*
keywords: Mycobacterium tuberculosis; autophagy; bactericidal response; cytokine signaling; lipid metabolism.; macrophage