Infection with enteric pathogensSalmonella typhimurium and Citrobacter rodentiummodulate TGF-beta/Smad signaling pathways in the intestine
Year: 2018
Type: article
Abstract: Salmonella and Citrobacter are gram negative, members of Enterobacteriaceae family that are important causative agents of diarrhea and intestinal inflammation. TGF-β1 is a pleiotropic multifunctional cytokine that has been implicated in modulating the severity of microbial infections. How these pathogens alter the TGF-β1 signaling pathways in the intestine is largely unknown. Streptomycin-pretreated C57BL/6J mouse model colonized with S. typhimurium for 8 hours (acute) and 4 days (chronic) infection and FVB/N mice infected with C. rodentium for 6 days were utilized. Results demonstrated an increase in TGF-β1 receptor I expression (p<0.05) in S. typhimurium infected mouse ileum at both acute and chronic post-infection vs control. This was associated with activation of Smad pathways as evidenced by increased phosphorylated (p)-Smad2 and p-Smad3 levels in the nucleus. The inhibitory Smad7 mRNA levels showed a significant up regulation during acute phase of Salmonella infection but no change at 4d post-infection. In contrast to Salmonella, infection with Citrobacter caused drastic downregulation of TGF receptor I and II concomitant with a decrease in levels of Smad 2, 3, 4 and 7 expression in the mouse colon. We speculate that increased TGF-β1 signaling in response to Salmonella may be a host compensatory response to promote mucosal healing; while C. rodentium decreases TGF-β1 signaling pathways to promote inflammation and contribute to disease pathogenesis. These findings increase our understanding of how enteric pathogens subvert specific aspects of the host-cellular pathways to cause disease.
Source: Gut Microbes
Institutions: University of Illinois Chicago, Jesse Brown VA Medical Center
Language: English
Topic: TGF-β signaling in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,060
Awards: G1094064403, G1265615842, G1372760518, G1428312052, G1820915188, G1845875378, G239151496, G2416016762, G273537122, G2945054892, G3210560845, G3227098983, G3356629308, G3420455245, G5526872009, Intestinal 5-HT Transporter: A novel therapeutic target for GI disorders, Probiotics: Potential Therapeutic Roles in Diarrhea, G6363864785, G6451628097, Chloride Transporter Downregulation in Infectious Diarrhea, Gut-liver crosstalk in bile-acid induced diarrhea, G8953752311
OpenAlex ID: W2790075448