A secreted sirtuin from Campylobacter jejuni contributes to neutrophil activation and intestinal inflammation during infection

Abstract

Histone modifications control numerous processes in eukaryotes, including inflammation. Some bacterial pathogens alter the activity or expression of host-derived factors, including sirtuins, to modify histones and induce responses that promote infection. In this study, we identified a deacetylase encoded by Campylobacter jejuni which has sirtuin activities and contributes to activation of human neutrophils by the pathogen. This sirtuin is secreted from the bacterium into neutrophils, where it associates with and deacetylates host histones to promote neutrophil activation and extracellular trap production. Using the murine model of campylobacteriosis, we found that a mutant of this bacterial sirtuin efficiently colonized the gastrointestinal tract but was unable to induce cytokine production, gastrointestinal inflammation, and tissue pathology. In conclusion, these results suggest that secreted bacterial sirtuins represent a previously unreported class of bacterial effector and that bacterial-mediated modification of host histones is responsible for the inflammation and pathology that occurs during campylobacteriosis.

Comparative Analysis of Rumen Microbiota Composition in Dairy Cows with Simple Indigestion and Healthy Cows

“…In addition, recent studies have found that Synergistes appears to be more prevalent in people with tooth and gum disease than in healthy people [42,43]. Both Clostridium and Campylobacter are associated with digestive tract disorders, with the former releasing an endotoxin causing mucosal necrosis [44,45] and the latter causing enteritis [46]. The increased abundance of these genera also suggests that inflammation may be present in the rumens of cows with indigestion.…”

Exploring the Contribution of Campylobacter jejuni to Post-Infectious Irritable Bowel Syndrome: A Literature Review

“…This sirtuin is secreted into neutrophils, where it binds to and deacetylates the host's histones, thereby fostering neutrophil activation and the generation of neutrophil extracellular traps (NETs). These NETs have been observed to concentrate within abscess formations in colonic crypts, suggesting a targeted immune response by neutrophils to C. jejuni within the intestinal environment [73]. These processes are instrumental in driving the inflammation and pathology observed in campylobacteriosis.…”

“…These processes are instrumental in driving the inflammation and pathology observed in campylobacteriosis. Interestingly, SliP's translocation into neutrophils is facilitated by the bacterium's flagella, suggesting a sophisticated mechanism of host interaction [73]. Upon secretion, SliP's association with neutrophil histones leads to diminished acetylation, directly influencing the host's epigenetic landscape.…”

“…Upon secretion, SliP's association with neutrophil histones leads to diminished acetylation, directly influencing the host's epigenetic landscape. Despite the mutant strain's efficient gastrointestinal tract colonization, SliP's presence is important for inducing inflammation and intestinal pathology [73], which highlights histone deacetylation by SliP as a novel pathway through which C. jejuni elicits inflammatory responses and contributes to tissue damage during infection.…”