Chemotherapy-Associated Changes of Histopathological Features of Mycobacterium ulcerans Lesions in a Buruli Ulcer Mouse Model

Suppressive effect of mycolactone-containing fraction from Mycobacterium ulcerans on antibody production against co-administered antigens

“…The inhibitory effect of mycolactone on the cytokine production could be linked to the suppression of antibody production, given that IL-4 is an important cytokine that induces Th 2 -type immune response. Interestingly, Ruf ulcerans in a mouse footpad model [20]. The accumulation of B cells could be caused by mycolactone, suggesting that mycolactone might also affect B cells directly or indirectly and disturb B cell activation and/ or differentiation into antibody-producing plasma cells.…”

“…ulcerans exists in extracellular area, unlike other intracellular mycobacteria such as M. tuberculosis [16,20]. Thus, specific antibodies to M. ulcerans might have a role in the clearance of M. ulcerans.…”

Corticosteroid-Induced Immunosuppression Ultimately Does Not Compromise the Efficacy of Antibiotherapy in Murine Mycobacterium ulcerans Infection

“…These so-called paradoxical reactions have been attributed to an exacerbated inflammatory response to mycobacterial antigens resulting from effective antibiotic activity [17], [23],[26]–28. In fact, several studies in humans and in mice have shown an increase of the local immune response during the antibiotic treatment, with abundant lymphocyte/macrophage infiltrates, in some cases forming organized lymphoid structures, and with the phagocytosis of bacilli [9], [20]–[22]. In addition, dead bacilli persist at the site of the treated lesion, which allows the maintenance of the inflammatory response [21].…”

“…Successful results for the treatment of nonulcerative and small ulcers have been described [14]–[17], but variation in efficacy has been reported for advanced and disseminated lesions, for which surgery is still required in combination with antibiotherapy to achieve healing [15]–[19]. Subsequent to RS treatment, both in humans and in the mouse model, the immunosuppressive state at the M. ulcerans foci of infection wanes over time, a process characterized by an increase in inflammatory infiltrates, phagocytic activity and development of organized lymphoid structures [9], [20]–[22], which, in turn, is associated with a rapid decline of viable bacteria [20], [21]. Additionally, during antibiotherapy in experimental infections it has been shown that the structure of the DLN is preserved, contributing for the establishment of a cellular immune response at the site of infection [21].…”

“…Despite the efficacy of the RS antibiotic regimen, acid fast-bacilli (AFB) persist at the site of infection for extended periods of time [9], [14], [20]–[26]. Although these AFB are non-viable, as suggested by the non-reactivation of experimental infections after corticosteroid administration, mice maintain an inflammatory response with active phagocytes at the site of infection [21].…”