Assessment of Cellular Immune Crosstalk of Lysogenic Salmonella Typhimurium with Chicken Macrophage

Introduction: The increased prevalence of antibiotic-resistant pathogenic bacteria has led to renewed attention to the use of bacteriophage as a potential antibacterial bioagent. Bacteriophage is a promising approach for the prevention and treatment of infectious diseases due to its effectiveness against antibiotic-resistant pathogens, specificity to the target pathogen, cost effectiveness to develop therapeutic system, and no serious side effects on eukaryotic host cells. However, there have been relatively few studies on the potential role of lysogens in reducing colonization of invading pathogens underlying the cellular and molecular immune responses.

Purpose: The objective of this study was to understand the role of lysogenic and lytic phages in the pathogenesis of intracellular Salmonella enterica serovar Typhimurium in chicken macrophages as measured by bacterial invasiveness and cellular immune response. 

Methods: The intracellular survival and invasive ability of nonlysogenic, lysogenic, and dual S. Typhimurium strains were evaluated at 37^oC for 24 h post-infection (h p.i.) in bacteriophage P22-post-treated and pre-treated HD-11 cells. The production of inflammatory factors (NO, TNF-α, IL-1β, IL-8, IL-6, and IL-10) was determined in the S. Typhimurium-infected HD-11 grown in the absence and presence of P22 at 1 and 24 h p. i. by using ELISA kits.

Results: The numbers of viable intracellular nonlysogenic, lysogenic, and dual Salmonella Typhimurium strains were significantly decreased to 8.1%, 31.8%, and 7.7%, respectively, in the infected HD11 cells grown with P22 for 24 h. The invading ability of S. Typhimurium strains into HD11 cells was effectively reduced by the pretreated-P22 at 1 h p.i. (> 2 log). The production of NO, TNF-α, IL-8, IL-6, and IL-10 was increased in HD11 cells in the presence of P22. The reduction of intracellular S. Typhimurium was highly correlated with the enhanced production of nitric oxide (NO) (r = 0.816, P < 0.001). 

Significance: These results suggest that the application of lysogenic bacteria and lytic phages could potentially be an effective way to control the survival of intracellular pathogen.