Increased Interleukin-1 (IL-1) and Imbalance between IL-1 and IL-1 Receptor Antagonist during Acute Inflammation in Experimental Shigellosis

Abstract

Infection by the enteric bacterial pathogen Shigella results in intense mucosal inflammation and destruction of the colonic and rectal epithelium in infected humans. Initial bacterial translocation occurs through the follicle-associated epithelium. Previous experiments suggest that interleukin-1 (IL-1) is crucial to trigger inflammation, particularly in the follicular zones. During the first 4 hours of infection in a rabbit ligated-loop model of intestinal invasion, there are two salient characteristics: (i) a high concentration of IL-1␣ and IL-1␤, both in infected Peyer's patch tissue and in the corresponding efferent mesenteric blood, and (ii) a very low level of expression of IL -1 receptor antagonist (IL-1ra). These may reflect a combination of regulation of expression and secretion of IL-1␣, IL-1␤, and IL-1ra by both resident and recruited phagocytes and the induction of mononuclear phagocyte apoptosis by Shigella. This low IL-1ra/IL-1 ratio likely accounts for the rapid, uncontrolled inflammation characteristic of shigellosis.

Shigella’s ways of manipulating the host intestinal innate and adaptive immune system: a tool box for survival?

“…Notably, bacterial invasion is also decreased, implying that IL-1-dependent inflammation facilitates bacterial invasion. 81 In support to this conclusion, the early inflammatory response in the murine lung model of infection was decreased in IL-1b knockout mice, compared with wild-type mice, yet bacterial clearance was similar. 79 Thus, in both models of infection, IL-1b is pro-inflammatory, but this inflammation is not beneficial for the host in terms of bacterial clearance or prevention of invasion.…”

Rupture, invasion and inflammatory destruction of the intestinal barrier by Shigella, making sense of prokaryote–eukaryote cross-talks

“…This con¢rms that a major function of IL-8 produced by epithelial cells is to attract PMNs to areas where bacterial invasion of the epithelium is occurring. Interestingly, neutralization of the function of IL-8 causes a spectacular decrease in the severity of epithelial lesions, but conversely allows passage of the bacteria in the lamina propria [61]. In consequence, the surface control of Shigella infection achieved by PMNs attracted along an IL-8 gradient occurs at the cost of severe epithelial destruction.…”

Early activation of mucosal dendritic cells and macrophages in acute Campylobacter colitis and cholera: An in vivo study

“…The high proportion of monocytes in shigellosis suggests recent recruitment of these cells from the blood stream. This possibility is supported by the findings of a study on rabbit ileal loops injected with Shigella flexneri in which large numbers of macrophages/monocytes were found in the subepithelial dome region over lymphoid follicles within 2–4 h of exposure to the pathogen 37 . The increased proportion of MPCs we saw in the deep mucosa of patients with acute shigellosis could be due to their migration from the superficial mucosa or due to their entry from submucosal vessels: similar to the way neutrophils enter the mucosa in rabbit ileal loops injected with Shigella flexneri 38 …”