Innate Immune Responses in Children and Adults with Shigellosis

Abstract

An array of pro-and anti-inflammatory mediators of the innate immune system was analyzed in stool, urine, and rectal mucosa samples from adults and children with shigellosis to better understand their role in recovery from and in the immunopathogenesis of the disease. Increased concentrations of lactoferrin (Lf), myeloperoxidase (MPO), prostaglandin E 2 , and leukotriene B 4 (LTB 4 ) in stool during acute shigellosis in both children and adults indicated that activated cells of the innate defense system at the mucosal site were secreting the mediators. Increased concentration of MPO and 8-iso-prostaglandin F 2␣ and lower levels of superoxide dismutase (SOD) activity in stool during acute Shigella infection suggested increased formation of reactive oxygen species, free radical-catalyzed peroxidation of membrane lipids, and decreased scavenging of the reactive oxygen radicals. In children, lower expression of SOD in tissue with severe inflammation and lower levels of SOD activity in stool for longer periods compared to adults may further worsen the tissue damage and predispose the children to a lowered defense. Both adult and pediatric patients had significantly higher expression of inducible nitric oxide synthase (iNOS) in the rectum with severe inflammation, compared to that seen with mild inflammation, accompanied by persistently up-regulated iNOS mRNA, reflecting increased production of nitric oxide at the local site. However, in contrast to adults, reduced urinary nitrate levels in pediatric patients during acute shigellosis suggested lower production of nitric oxide in the renal compartment.

Impaired Resistance and Enhanced Pathology During Infection with a Noninvasive, Attaching-Effacing Enteric Bacterial Pathogen,Citrobacter rodentium, in Mice Lacking IL-12 or IFN-γ

“…However, iNOS expression is not restricted to phagocytes. Increased iNOS expression has been reported in colonic epithelial cells of patients with inflammatory bowel disease or acute Shigella colitis (29,30). Furthermore, in polarized colonic epithelial cells infected with pathogenic E. coli, the stable NO end products, nitrate and nitrite, are preferentially located on the apical side, suggesting that epithelial cell-derived NO and its metabolites might affect pathogens on the lumenal side of the epithelium (31).…”

Prevention of Intestinal Infection by Glycomacropeptide

“…Desialylation of GMP was confirmed by the periodate-resorcinol method. 16) Periodate oxidation of GMP was performed according to the method of Raqib et al 17) A GMP solution (5 mg/1 ml of a 0.1 M acetate buffer containing 50 mM sodium periodate (pH 5.5)) was incubated in the dark for 20 min. After dialyzing against distilled water, the solution was lyophilized.…”

Shigella impairs T lymphocyte dynamics in vivo

“…Natural infection fails to elicit a long-lasting protective immunity, and several infection episodes are required to generate a short-term, mainly antibody-mediated protection (6,7). This suggests that Shigella has evolved strategies to dampen the acquired immune response.…”