title: Apoptosis in acute shigellosis is associated with increased production of Fas/Fas ligand, perforin, caspase-1, and caspase-3 but reduced production of Bcl-2 and interleukin-2.
abstract: Shigella dysenteriae type 1-induced apoptotic cell death in rectal tissues from patients infected with Shigella dysenteriae type 1 was studied by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and annexin V staining. Expression of proteins and cytokines participating in the apoptotic process (caspase-1, caspase-3, Fas [CD95], Fas ligand [Fas-L], perforin, granzyme A, Bax, WAF-1, Bcl-2, interleukin-2 [IL-2], IL-18, and granulocyte-macrophage colony-stimulating factor) in tissue in the acute and convalescent stages of dysentery was quantified at the single-cell level by in situ immunostaining. Apoptotic cell death in the lamina propria was markedly up-regulated at the acute stage (P < 0.05), where an increased number of necrotic cells were also seen. Phenotypic analysis of apoptotic cells revealed that 43% of T cells (CD3), 10% of granulocytes (CD15), and 5% of macrophages (CD56) underwent apoptosis. Increased activity of caspase-1 persisted in the rectum up to 1 month after onset. More-extensive expression of Fas, Fas-L, perforin, caspase-3, and IL-18, but not IL-2, at the acute stage than at the convalescent stage was observed. Increased expression of caspase-3 and IL-18 in tissues with severe inflammation compared to expression in those with mild inflammation was evident, implying a possible role in the perpetuation of inflammation. Significantly reduced cell death during convalescence was associated with a significant up-regulation of Bcl-2, Bax, and WAF-1 expression in the rectum compared to that in the acute phase of infection. Thus, induction of apoptosis at the local site in the early phase of S. dysenteriae type 1 infection was associated with a significant up-regulation of Fas/Fas-L and perforin and granzyme A expression and a down-regulation of Bcl-2 and IL-2, which promote cell survival.
authors: International Centre for Diarrhoeal Diseases Research, Bangladesh, Dhaka, Bangladesh. rubhana@icddrb.org
authors: Rubhana
authors: R
authors: Raqib
authors: Caroline
authors: C
authors: Ekberg
authors: Protim
authors: P
authors: Sharkar
authors: Pradip K
authors: PK
authors: Bardhan
authors: Arturo
authors: A
authors: Zychlinsky
authors: Philippe J
authors: PJ
authors: Sansonetti
authors: Jan
authors: J
authors: Andersson
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D020170:Caspase 1 / Q000096:biosynthesis*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004405:Dysentery, Bacillary / Q000276:immunology* / Q000473:pathology; D053222:Fas Ligand Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D053804:Granzymes; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D009336:Necrosis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012007:Rectum / Q000166:cytology / Q000276:immunology; D012697:Serine Endopeptidases / Q000096:biosynthesis; D012762:Shigella dysenteriae / Q000276:immunology*; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000096:biosynthesis*
chemical_list: C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D054353:Perforin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1