To Achieve an Earlier IFN-γ Response Is Not Sufficient to Control Mycobacterium tuberculosis Infection in Mice

The temporo-spatial relationship between the three organs (lung, spleen and lymph node) involved during the initial stages of Mycobacterium tuberculosis infection has been poorly studied. As such, we performed an experimental study to evaluate the bacillary load in each organ after aerosol or intravenous infection and developed a mathematical approach using the data obtained in order to extract conclusions. The results showed that higher bacillary doses result in an earlier IFN-gamma response, that a certain bacillary load (BL) needs to be reached to trigger the IFN-gamma response, and that control of the BL is not immediate after onset of the IFN-gamma response, which might be a consequence of the spatial dimension. This study may have an important impact when it comes to designing new vaccine candidates as it suggests that triggering an earlier IFN-gamma response might not guarantee good infection control, and therefore that additional properties should be considered for these candidates.