Persistence of Mucosal Mast Cells and Eosinophils inShigella-Infected Children

Abstract

Cells of the innate immune system and their mediators were studied at the single-cell level in the rectums of pediatric and adult patients with Shigella infection to better understand why children are at higher risk for severe infection. Adult patients had increased infiltration of mucosal mast cells (MMC) at the acute stage (3 to 5 days after the onset of diarrhea) and eosinophils in early convalescence (14 to 16 days after onset). Increased expression of stem cell factor and prostaglandin H synthase-1 (PGHS-1) was associated with increased tryptase-K i 67-double-positive MMC in the acute stage and increased apoptosis of MMC, which led to a rapid decline in early convalescence. The eosinophils demonstrated increased expression of major basic protein (MBP), eotaxin, and CCR3, as well as increased necrotic death. The neutrophils showed enhanced ␣-defensin and lactoferrin expression in the acute phase. In contrast to adults, the pediatric patients demonstrated delayed accumulation of mast cells and eosinophils, while ␣-defensin expression persisted during convalescence. In contrast, neutrophil counts and lactoferrin expression were reduced in children compared to adults. The results suggest that children with shigellosis have a persistent activation of the innate immune response in the convalescent phase, indicating delayed elimination of Shigella antigens compared to adults.

Association of EnterotoxigenicBacteroides fragilisInfection with Inflammatory Diarrhea

“…Similarly, ETBF and B. fragilis toxin stimulate fluid secretion and mixed cellularity inflammation when tested in ligated small bowel and colonic segments in animal models [34–36]. When compared with data reported on intestinal inflammation detected in the stool samples of Bangladeshi patients infected with enterotoxigenic E. coli, V. cholerae, or Shigella species, ETBF infection stimulates a greater stool inflammatory response than does enterotoxigenic E. coli or V. cholerae but generally causes less marked inflammation than does Shigella infection (data not shown) [37–39]. Our results are a reminder that the origin and pathogenesis of most diarrheal illnesses cannot be predicted at the bedside without specific microbiology and other laboratory studies.…”

Acute dehydrating disease caused by Vibrio cholerae serogroups O1 and O139 induce increases in innate cells and inflammatory mediators at the mucosal surface of the gut

“…35 Thus higher levels of C reactive protein in blood (p = 0.03), and TNF-a and IL-1b in stool (p,0.001), were detected in patients with bloody dysentery. It is interesting however that mast cells and eosinophils, including other innate mediators, are in general comparable in shigellosis 36 and cholera. In contrast, in shigellosis, these factors may be protective but may also contribute to immunopathogenesis at the local site.…”

Eosinophils in infection and intestinal immunity

“…There is evidence to support increased numbers of eosinophils during bacterial infection. For example, eosinophil levels in the peripheral blood and rectum of patients afflicted with the diarrheal-inducing pathogen Shigella are increased [95]. However, a prominent role for eosinophils in clearing infections remains uncertain as a marked decrease in circulating eosinophils, or eosinopenia, has long been associated with acute bacterial infections in patients [96].…”