Transcriptional profile of Mycobacterium tuberculosis replicating in type II alveolar epithelial cells.

摘要: Mycobacterium tuberculosis (M. tb) infection is initiated by the few bacilli inhaled into alveolus. Studies in lungs of aerosol-infected mice provided evidence for extensive replication M. tb non-migrating, non-antigen-presenting cells alveoli during first 2–3 weeks post-infection. Alveoli are lined type II and I alveolar epithelial (AEC) which outnumber macrophages several hundred-fold. DNA viable have been demonstrated AEC other non-macrophage kidney, liver, spleen autopsied tissues from latently-infected subjects TB-endemic regions indicating systemic bacterial dissemination primary infection. also to replicate rapidly A549 (type line) acquire increased invasiveness endothelial cells. Together, these results suggest that could provide an important niche expansion development a phenotype promotes In current studies, we compared transcriptional profile replicating intracellularly laboratory broth, microarray analysis. Genes significantly upregulated intracellular residence were consistent with active, replicative, metabolic, aerobic state, as genes tryptophan synthesis virulence (ESAT-6, ESAT-6-like genes, esxH, esxJ, esxK, esxP, esxW). contrast, significant downregulation DevR (DosR) regulon hypoxia-induced was observed. Stress response either not differentially expressed or downregulated exception heat shock those induced low pH. The intra-type transcriptome strongly suggests safe haven can expand dramatically disseminate lung prior elicitation adaptive immune responses.