Peroxide in a cell is formed by the NADPH oxidase, a multicomponent enzyme system responsible for releasing reactive oxygen species in a process known as the respiratory burst. A voluminous literature exists pertaining to the role of ROS in regulating antigen presentation. ROS mediated maintenance of the intracellular redox potential of macrophages and DCs is crucial for their antigen presenting capability. In addition, it is also reported that antigen specific bidirectional dendritic cell and T cell interaction is blocked by inhibiting NADPH oxidase due to inhibition of ROS productio. In addition, published data suggest that phagocyte NADPH oxidase prevents acidification of the phagosomes and thereby promote antigen cross presentation. Thus, it can be clearly concluded that by modulating the ROS profile of an AP24534 infected host, its antigen presentation capacity can be altered. In this study, we sought to examine whether CpG-DNA treatment can bring about the growth attenuation of Salmonella in DCs and to identify the mechanisms involved in the antibacterial response of CpG-DNA treated DCs. We further hypothesized that CpG induced ROS can enhance the antigen presentation capacity of the Salmonella infected DCs and can therefore alter the fate of the infection. We observed that CpG DNA treatment inhibits Salmonella Typhimurium growth in murine DCs in a ROS dependent manner. Further, our study unravels the role of ROS in promoting antigen presentation in Salmonella infected DCs. An enhanced antigen presentation was seen in the Salmonella infected dendritic cells upon CpG treatment. Salmonella infected cells showed a decrease in the allogenic T cell proliferation than the control cells. However, Salmonella could not decrease the CpG induced enhanced T cell proliferation. Hence, it can be concluded that Salmonella utilizes the unique strategy of inhibiting the DC mediated antigen presentation. However, activating the host innate receptor TLR-9 allows an efficient presentation of Salmonella. Further, CpG treated DCs when injected in the mice system could reduce the Salmonella load from various organs suggesting this result can be extrapolated in vivo as well. Thus, our data identifies a strategy to increase the efficiency of antigen presentation by Salmonella infected DCs. The intracellular life of Salmonella in the DC is very interesting. Salmonella does not get killed or proliferate in the DC population. Intracellular survival of S. Typhimurium in murine DC was independent from the function of virulence factors known to be important for survival in macrophages, such as the SPI2-T3SS. Surprisingly, the bacterial LPS O antigen is found to be very crucial to maintain bacterial steady burden in the DCs.