Altogether, these observations in human studies suggest that a CMI response would associate with the activity of the antibiotics. However, since in the previous studies no direct correlations were addressed between alterations in histology and bacterial viability in the same subjects, it remains unclear whether the immune recuperation associated with efficient antibiotherapy begins before or after the elimination of viable bacilli, which depends on the timing of the host response not only in the infection focus but also in the DLN. In addition, persistence of acid fast bacilli in the lesions has been reported after the end of the treatment period, in both mice and in humans, raising the question of M. ulcerans being dead or only in a state of latency, as reported for Mycobacterium tuberculosis. This may have implications for our understanding on the worsening of lesions or the appearance of new lesions reported in RS-treated patients Octinoxate during or after treatment, the so-called paradoxical reactions, that may be triggered either by M. ulcerans antigens or by viable organisms. We have therefore studied in the mouse footpad model of M. ulcerans infection, during and after a RS regimen, the progression of the infection, viability and eradication of bacteria, as well as the dynamics of the cellular host immune responses in both the footpad and the DLN. Since the recommendation by WHO in 2004 of treating BU patients with a regimen of antibiotherapy combining RS, clinical studies gave rise to the hypothesis that a synergistic effect between antibiotics and the host immune system is in place to clear M. ulcerans infection. RS are bactericidal against extracellular and intramacrophage susceptible mycobacteria and the quick reduction in M. ulcerans CFU counts in treated mice suggests that such mode of antimycobacterial activity also operates in vivo. However, the possible participation of the host immune system in the control of the infectious process remains an open question. Considering the limitations of human studies, experimental infections performed in animal models constitute a crucial contribution for a detailed investigation on the host immune response to M. ulcerans during antibiotherapy. This approach may well open the possibility of immune-based interventions for the treatment of BU as an alternative or a complement to the current RS protocol. Indeed, the WHO RS protocol presents several limitations, including the insufficient response of advanced lesions, the long period of administration of intramuscular streptomycin leading to poor compliance as it demands skilled personnel and is accompanied by adverse side Cantharidin effects , and the occurrence of paradoxical reactions characterized by the worsening of lesions or the appearance of new lesions.