Lactobacillus Crispatus Strain SJ-3C-US Induces Human Dendritic Cells (DCs) Maturation and Confers an Anti-inflammatory Phenotype to DCs

Lactobacillus crispatus is one of the most predominant species in the healthy vagina microbiota. Nevertheless, the interactions between this commensal bacterium and the immune system are largely unknown. Given the importance of the dendritic cells (DCs) in the regulation of the immunity, this study was performed to elucidate the influence of vaginal isolated L. crispatus SJ-3C-US from healthy Iranian women on DCs, either directly by exposure of DCs to ultraviolet-inactivated (UVI) and heat-killed (HK) L. crispatus SJ-3C-US or indirectly to its cell-free supernatant (CFS), and the outcomes of immune response. In this work we showed that L. crispatus SJ-3C-US induced strong dose-dependent activation of dendritic cells and production of high levels of IL-10, whereas IL-12p70 production was induced at low level in an inverse dose-dependent manner. This stimulation skewed T cells polarization toward CD4(+) CD25(+) FOXP3(+) Treg cells and production of IL-10 in a dose-dependent manner in mixed leukocyte reaction (MLR) test. The mode of bacterial inactivation did not affect the DCs activation pattern, upon encounter with L. crispatus SJ-3C-US. Moreover, while DCs stimulated with CFS showed moderate phenotypic maturation and IL-10 production, it failed to skew T cells polarization toward CD4(+) CD25(+) FOXP3(+) regulatory T cells (Treg) and production of IL-10. This study showed that L. crispatus SJ-3C-US confers an anti-inflammatory phenotype to DCs through up-regulation of anti-inflammatory/regulatory IL-10 cytokine production and induction of CD4(+) CD25(+) FOXP3(+) T cells at optimal dosage. Our findings suggest that L. crispatus SJ-3C-US could be a potent candidate as protective probiotic against human immune-mediated pathologies, such as chronic inflammation, vaginitis or pelvic inflammatory disease (PID).