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closeReferee comments: Referee 2
Posted by PLOS_ONE_Group on 04 Jan 2008 at 14:48 GMT
Referee 2's review:
This is a conceptually straightforward study of host cell and bacterial gene expression responses when M. tuberculosis infects human blood-derived macrophages and dendritic cells. For the most part, the studies were well done and well-controlled; the results contain few surprises, and indicate that M. tuberculosis senses different environments within cultured macrophages and DCs.
1. Figure 4C is both poorly labeled and seems to have some implausible results. The ordinate is neither arithmetic nor logarithmic; as a consequence, the extent of bacterial multiplication is impossible to discern. In particular, on day 3 postinfection, there are somewhere between 1x10e5 and 5x10e6 bacteria per 100,000 macrophages. If one speculates that it's about 1 x 10e6, then the bacterial population expanded 25-fold in the ensuing 2 days, which is far more rapid than the usual growth rate of M. tuberculosis. Moreover, the day 5 value (2.5 x 10e7 per 100,000 macrophages) indicates an average of 250 bacteria per macrophage, which is also difficult to accept as accurate.
2. While annotation and clustering algorithms and terminology are not necessarily the inventions of the authors, some thought needs to go into the presentation of the data in Figure 2B. In particular, functional categories titled, "Pathogenic E. coli infection-EPEC" and "Pathogenic E. coli infection-EHEC" are not useful to a reader without additional information - perhaps these and several of the other less obvious functional categories could be annotated with citations referencing the genes in such functional categories.
3. Information on the strain of M. tuberculosis used and how it has been passaged and selected to maintain its virulence need to be provided, for the sake of comparing the results reported here to those of past and future studies.
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N.B. These are the general comments made by the reviewer when reviewing this paper in light of which the manuscript was revised. Specific points addressed during revision of the paper are not shown.