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The outcome of many infections depends on the initial interactions between agent and host. Aiming at elucidating the effect of the  M. tuberculosis  Mce1 protein complex on host transcriptional and immunological responses to infection with  M. tuberculosis , RNA from murine macrophages at 15, 30, 60 min, 4 and 10 hrs post-infection with  M. tuberculosis  H37Rv or Δ- mce1  H37Rv was analyzed by whole-genome microarrays and RT-QPCR. Immunological responses were measured using a 23-plex cytokine assay. Compared to uninfected controls, 524 versus 64 genes were up-regulated by 15 min post H37Rv- and Δ- mce1  H37Rv-infection, respectively. By 15 min post-H37Rv infection, a decline of 17 cytokines combined with up-regulation of  Ccl24  (26.5-fold),  Clec4a2  (23.2-fold) and  Pparγ  (10.5-fold) indicated an anti-inflammatory response initiated by IL-13. Down-regulation of  Il13ra1  combined with up-regulation of  Il12b  (30.2-fold), suggested switch to a pro-inflammatory response by 4 hrs post H37Rv-infection. Whereas no significant change in cytokine concentration or transcription was observed during the first hour post Δ- mce1  H37Rv-infection, a significant decline of IL-1b, IL-9, IL-13, Eotaxin and GM-CSF combined with increased transcription of  Il12b  (25.1-fold) and  Inb1  (17.9-fold) by 4 hrs, indicated a pro-inflammatory response. The balance between pro-and anti-inflammatory responses during the early stages of infection may have significant bearing on outcome.

Modulation of Transcriptional and Inflammatory Responses in Murine Macrophages by the Mycobacterium tuberculosis Mammalian Cell Entry (Mce) 1 Complex