Immune evasion and survival strategies of evolved hyper-virulent Salmonella Typhimurium strains

Abstract

Introduction: Salmonella is a Gram-negative, rod-shaped bacteria which causes millions of death worldwide due to gastroenteritis and typhoid fever in humans and animals. The mortality of Salmonella infection has gradually increased because of the emergence of antibiotic-resistant strains such as multidrug-resistant (MDR) and extremely drug-resistant (XDR). The multiple host-pathogen and non-host environment help in the emergence of multidrug-resistance and hypervirulent strains. Our previous study showed Salmonella Typhimurium (STM) adaptation to different in-vitro and in-vivo, and evolved into hypervirulent strains P12-STM, Ce12-STM, and F12-STM. This study deals with the mechanism of immune evasion strategies of these three strains and how they become hypervirulent and hyperproliferative inside mouse macrophage RAW-264.7. Methodology: Real-time PCR, western blotting, and confocal microscope were used to check the immune evasion and alteration of signaling pathways by the hyper-virulent strains. Results: The hypervirulent strains create an anti-inflammatory environment inside Raw-264.7 by altering cytokine production via NF-κB and Akt-NLRC4 signaling for their better survival inside mouse macrophage. The strain also reduced the lysosome-phagosome fusion for better survival in comparison to unpassaged wild-type strain. Conclusion: The evolved hypervirulent Salmonella strains reduce the host inflammatory response by resulting in an anti-inflammatory environment by upregulating IL-10 and down-regulating IL-1β expression. Upon inhibition of NF-κB and Akt signaling, the cytokine expression and bacterial burden inside mouse macrophages reverted, which suggests that these hypervirulent strains modulate the host immune system through these pathways.