7 ± 258 pg/mL vs. UV = 676.8 ± 124 pg/mL; p = n.s.). There are both quantitative and qualitative differences between monocytes from newborns and adults. Qualitative differences buy EPZ-6438 are evident in utero, as human fetal circulating monocytes reveal reduced levels of MHC class II molecules. Also, the addition of endotoxin to whole cord blood from human newborns results in diminished production of TNF when compared with adult peripheral blood [19]. Indeed, newborn-derived

monocytes cultured in whole blood or purified and cultured in autologous, newborn blood plasma show a 1-3-log impairment in TNF production in response to agonists of toll-like receptors [Reviewed by 16]. Thus, it has been confirmed that cells from umbilical cord produce fewer cytokines, such TNF-α, when compared to adult cells [19]. Another pattern was found when studying

MMP-9 levels induced by BCG-infected monocytes. MMP-9 is a metalloproteinase with pro-inflammatory properties and some specific functions, such as a reducing response to IL-2, generating similar fragments of angiostatin, having a high affinity for collagen, and stimulating secretion of cytokines, among them TNF-α and IL-1β [20]. Strikingly, virtually no production was found only in the naïve group, but again BCG was not able to distinguish resting, baseline levels found in the HD group. This observation can also be explained by circulating immature cells of the naïve group, as opposed to the already sensitized Z-VAD-FMK cost adults, to promptly produce MMP-9. As expected, this pattern was in agreement with the in-gel gelatin data, although those techniques are not related, and thus, the results are not directly compared

because they have distinct sensitivities. On the other Tryptophan synthase hand, Quiding-Jarbrink and colleagues in 2001 [20] showed increasing rates of MMP-9, but this may be related to different MOI ratio between theirs and the present study (10:1 vs. 2:1 respectively). In summary, one could conclude that the necrosis pattern found in monocytes from naïve group correlates well with IL-1β levels, but not with TNF-α and MMP-9, induced when those cells are BCG infected. Additional studies are warranted to rule out other mechanisms, such as pyroptosis. These findings support the hypothesis that BCG Moreau strain induces distinct cell-death patterns involving maturation of the immune system and that this pattern might set the stage for a subsequent antimycobacterial immune response, which may have profound effects during vaccination. The authors are grateful to Dr. Stuart Krassner (UCI, Irvine, USA) for text editing. We also thank Paulo Redner and Ariane L. de Oliveira (Leprosy Laboratory, IOC/FIOCRUZ), and Luana T.A. Guerreiro and Prof. Dasio Marcondes (Gaffree Guinle State University Hospital) for their help during technical procedures.