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Chronic Salmonella Infection Induced Intestinal Fibrosis
Published on: September 22, 2019
Anti-inflammatory properties of probiotic bacteria on Salmonella-induced IL-8 synthesis in enterocyte-like Caco-2
J J Malago1, P C J Tooten, J F J G Koninkx
1Department of Pathology, Faculty of Veterinary Medicine, Sokoine University of Agriculture, Chuo Kikuu, Morogoro, Tanzania.
Abstract:
Invasion of the gut by pathogenic Salmonella leads to production of IL-8 that initiates inflammatory reactions to combat the bacterium. However, its persistent production causes tissue damage and interventions that suppress IL-8 production prevent tissue damage. We hypothesised that probiotics could mediate their benefits via inhibition of IL-8 synthesis. Caco-2 cells were infected with probiotic Bifidobacterium infantis W52, Lactobacillus casei W56, Lactococcus lactis W58, Lactobacillus acidophilus W70, Bifidobacterium bifidum W23, or Lactobacillus salivarius W24 or pathogenic Salmonella enterica serovar Enteritidis 857 at 0, 0.2, 1, 2, 10, 20, 100 or 200 bacterial cells/Caco-2 cell for 1 hour. Cells were also exposed to a combination of one probiotic bacterium (200 bacterial cells/Caco-2 cell) and the graded numbers of Salmonella as either co-incubation (1 hour) or pre-incubation of the probiotic bacterium (1 hour) followed by Salmonella (1 hour). The cells recovered for 2 or 24 hours. IL-8 and Hsp70 were determined by ELISA and Western blot respectively. Both probiotics and Salmonella induced a dose- and time-dependent synthesis of IL-8 but probiotics induced far lower IL-8 levels than Salmonella. The Salmonella-induced IL-8 was significantly suppressed by B. infantis W52, L. casei W56 and L. lactis W58 at low numbers of Salmonella (0.2 to 20 bacterial cells/Caco-2 cell) and within 2 hours of recovery. The observed probiotic-mediated reduction in IL-8 secretion was transient, and lost after a few hours. In addition, these three probiotics induced a significant increase in Hsp70 expression while L. acidophilus W70, B. bifidum W23 and L. salivarius W24 induced a weak Hsp70 expression and could not suppress the Salmonella-induced IL-8 synthesis. We conclude that suppression of Salmonella-induced IL-8 synthesis by Caco-2 cells is exhibited by probiotics that induce expression of Hsp70, suggesting that the protective role of probiotics could be mediated, at least in part, via Hsp70 expression. This suppression is limited to a low number of infecting pathogenic Salmonella.
Insights
Certain probiotics, like Bifidobacterium infantis W52, can transiently suppress Salmonella-induced IL-8 (interleukin-8) production in gut cells. This protective effect is linked to increased Hsp70 expression and is most effective against low pathogen loads.
Area of Science:
- Gut Microbiome Research
- Immunology
- Cell Biology
Background:
- Pathogenic Salmonella invades the gut, triggering IL-8 (interleukin-8) production, which causes inflammation and tissue damage.
- Persistent IL-8 production contributes to gut tissue damage, making IL-8 suppression a therapeutic target.
- Probiotics are investigated for their potential to modulate gut inflammation by inhibiting IL-8 synthesis.
Purpose of the Study:
- To investigate the hypothesis that probiotics can reduce gut inflammation by inhibiting IL-8 synthesis.
- To determine if specific probiotic strains can suppress Salmonella-induced IL-8 production in Caco-2 cells.
- To explore the role of Heat Shock Protein 70 (Hsp70) in mediating probiotic effects on IL-8 synthesis.
Main Methods:
- Caco-2 cells were infected with various probiotic strains (Bifidobacterium infantis W52, Lactobacillus casei W56, Lactococcus lactis W58, etc.) and Salmonella enterica serovar Enteritidis.
- Cells were exposed to probiotics and Salmonella in co-incubation or pre-incubation models, followed by recovery periods of 2 or 24 hours.
- Interleukin-8 (IL-8) and Heat Shock Protein 70 (Hsp70) levels were quantified using ELISA and Western blot, respectively.
Main Results:
- Both probiotics and Salmonella induced dose- and time-dependent IL-8 synthesis, with Salmonella inducing significantly higher levels.
- B. infantis W52, L. casei W56, and L. lactis W58 significantly suppressed Salmonella-induced IL-8 at low pathogen loads (0.2-20 cells/Caco-2 cell) within 2 hours.
- These three probiotic strains also significantly increased Hsp70 expression, while other tested probiotics showed weaker Hsp70 induction and failed to suppress IL-8.
- The observed IL-8 suppression by probiotics was transient, diminishing after a few hours.
Conclusions:
- Probiotic-mediated suppression of Salmonella-induced IL-8 synthesis in Caco-2 cells is strain-specific and linked to Hsp70 expression.
- Specific probiotics (B. infantis W52, L. casei W56, L. lactis W58) may protect against Salmonella-induced gut inflammation partly through Hsp70 induction.
- The protective effect is limited to low numbers of infecting Salmonella and is transient.
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