Differential dendritic immune cell responses to infection with various serotypes of Shigella

Purpose: Dendritic cells (DC) are key regulators of immune response with the ability to affect both the innate and adaptive immune responses and are abundant in the gut mucosa. The severity of shigellosis varies with the serotype involved with S. dysenteriae producing the severest infections with complications and S. sonnei being at the other end of spectrum usually causing mild self-limiting diarrhea. While Shigella are known to induce the apoptosis of mature DCs, there is no information on cytokine milieu of DCs incubated with different serotypes of Shigella. Methods: Monocyte derived dendritic cells (MoDCs) were developed from healthy human PBMC after 8 days of culture. DCs were infected with different Shigella serotypes. After 24 h post infection, relative expression of cytokines IL-1 beta, IL-6, IL-8, TNF-alpha, IL-12p70, IL-17, IL-22 and IL-23 was studied by Real Time PCR and cytometric bead arrays (CBA). Results: We found that different serotypes of Shigella significantly stimulated production of IL-1 beta, IL-6, IL-8, IL-12, IL-23, INF-gamma and TNF-alpha compared to uninfected DCs and there were significant differences among these serotypes. At transcriptional level, highest levels of expression of IL-1 beta, IL-6, IL-8, TNF-alpha, IFN-gamma, IL-17, IL-22 and IL-23 were observed in S. dysenteriae infected DCs. Significant serotypic differences were noted between S. dysenteriae & S. flexneri and between S. dysenteriae & S. sonnei. Conclusions: DCs are critical sentinel cells that relay microbial presence either directly or indirectly to naive T cells. In this study we found that S. dysenteriae caused maximum expression of pro-inflammatory cytokines. Similarly, S. dysenteriae also caused highest expression of IL-17A and IL-22A. It was the only serotype, which increased IL-23. These findings could explain more severity of SD as compared to SF and SS.