Abstract
High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein that can be actively secreted by immune cells after different immune stimuli or passively released from cells undergoing necrosis. HMGB1 amplifies inflammation, and its hypersecretion contributes to multiple organ dysfunction syndrome and death. We tested possible immunomodulatory effect of commensal Lactobacillus amylovorus (LA), Lactobacillus mucosae (LM) or probiotic Escherichia coli Nissle 1917 (EcN) in infection of gnotobiotic piglets with Salmonella Typhimurium (ST). Transcription of HMGB1 and Toll-like receptors (TLR) 2, 4, and 9 and receptor for advanced glycation end products (RAGE), TLR4-related molecules (MD-2, CD14, and LBP), and adaptor proteins (MyD88 and TRIF) in the ileum and colon were measured by RT-qPCR. Expression of TLR4 and its related molecules were highly upregulated in the ST-infected intestine, which was suppressed by EcN, but not LA nor LM. In contrast, HMGB1 expression was unaffected by ST infection or commensal/probiotic administration. HMGB1 protein levels in the intestine measured by ELISA were increased in ST-infected piglets, but they were decreased by previous colonization with E. coli Nissle 1917 only. We conclude that the stability of HMGB1 mRNA expression in all piglet groups could show its importance for DNA transcription and physiological cell functions. The presence of HMGB1 protein in the intestinal lumen probably indicates cellular damage.
Highlights
High mobility group box 1 (HMGB1) is an intracellular nuclear DNA-binding protein that can be produced by innate immune cells or released from cells undergoing necrosis [1]
Our work aimed to describe intestinal HMGB1 release after infection of gnotobiotic piglets with Gram-negative enteric pathogen Salmonella Typhimurium, signaling via TLR2, Toll-like receptor 4 (TLR4), TLR9, and receptor for advanced glycation end products (RAGE), and the possible influence of previous colonization of the piglets with commensal Gram-positive lactobacilli Lactobacillus amylovorus and Lactobacillus mucosae or probiotic Gram-negative E. coli Nissle 1917
TLR4 is the common point of LPS and HMGB1 signaling pathways, because TLR4 is the receptor for both molecules [5,21] and HMGB1 potentiates the inflammatory effects of LPS [64]
Summary
High mobility group box 1 (HMGB1) is an intracellular nuclear DNA-binding protein that can be produced by innate immune cells or released from cells undergoing necrosis [1]. Despite the fact that Lactobacillus spp. are typically beneficial for the host, care should be taken with their application in immunocompromised hosts [43] and all new probiotic bacteria should be tested for their antimicrobial susceptibility [44] Some lactobacilli strains, such as L. rhamnosus GG, L. casei Shirota, and L. acidophilus LB, are widely used probiotics [45], and commensal lactobacilli strains have been used to combat enteric pathogens [46,47]. Our work aimed to describe intestinal HMGB1 release after infection of gnotobiotic piglets with Gram-negative enteric pathogen Salmonella Typhimurium, signaling via TLR2, TLR4, TLR9, and RAGE, and the possible influence of previous colonization of the piglets with commensal Gram-positive lactobacilli Lactobacillus amylovorus and Lactobacillus mucosae or probiotic Gram-negative E. coli Nissle 1917.
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