Abstract
Shigella dysenteriae type 1 causes devastating epidemics in developing countries with high case-fatality rates in all age-groups. The aim of the study was to compare host immune responses to epidemic (T2218) and endemic strains of S. dysenteriae type 1. Shigellacidal activity of serum from rabbits immunized with epidemic or endemic strains, S. dysenteriae type 1-infected patients, and healthy adult controls from Shigella-endemic and non-endemic regions was measured. Immunogenic cross-reactivity of antibodies against Shigella antigens was evaluated by Western blot analysis. Oxidative burst and phagocytic responses of monocytes and neutrophils to selected S. dysenteriae type 1 strains were assessed by flow cytometry. Rabbit antisera against epidemic strain were less effective in killing heterologous bacteria compared to endemic antisera (p=0.0002). Patients showed an increased serum shigellacidal response after two weeks of onset of diarrhoea compared to the acute stage (3-4 days after onset) against their respective homologous strains; the response against T2218 and heterologous endemic S. dysenteriae type 1 strains was not significant. The serum shigellacidal response against all the S. dysenteriae type 1 strains was similar among healthy controls from endemic and non-endemic regions and was comparable with the acute stage response by patients. Compared to endemic strains of S. dysenteriae type 1, T2218 was significantly resistant to phagocytosis by both monocytes and neutrophils. No obvious differences were obtained in the induction of oxidative burst activity and cathelicidin-mediated killing. Cross-reactivity of antibody against antigens present in the epidemic and endemic strains showed some differences in protein/peptide complexity and intensity by Western blot analysis. In summary, epidemic T2218 strain was more resistant to antibody-mediated defenses, namely phagocytosis and shigellacidal activity, compared to endemic S. dysenteriae type 1 strains. Part of this variation may be attributed to the differential complexity of protein/peptide antigens.
Highlights
The shigellacidal response of patient sera against the respective homologous S. dysenteriae type 1 strains was significantly higher on day 11 compared to day 1 (p=0.05) (Fig. 1); the response reduced on day 30 but still remained higher than day 1
Data are expressed as mean±sandard error of mean (SEM); DCF=Dichloro-fluorescence; EnSd1=Endemic S. dysenteriae type 1; EpSd1=Epidemic S. dysenteriae type 1; fluorescein isothiocyanate (FITC)=Fluorescein isothiocyanate; mean fluorescence intensity (MFI)=Mean fluorescence intensity; SEM=Standard error of mean (Lane 3 and 5 of Fig. 4) but not in the endemic strain
The results of the study showed that the epidemic strain of S. dysenteriae type 1 mounted lower levels of shigellacidal serum antibodies and was more resistant to phagocytosis by neutrophils and monocytes compared to the endemic strains
Summary
According to the recent report of the World Health Organization on the worldwide burden of shigellosis, 90 million cases of diarrhoea due to Shigella occur annually mostly in developing countries, and an estimated 108,000 deaths per year. Four species of Shigella are responsible for causing bacillary dysentery: Shigella dysenteriae, S. flexneri, S. sonnei, and S. boydii. S. dysenteriae type 1 produces the most severe form of disease with a high mortality rate in young children, elderly people, and the malnourished and can be associated with various complications [1,2]. Since the 1960s, S. dysenteriae type 1 is known to be an important cause of epidemic dysentery in Latin America, Africa, and Asia, including Bangladesh [1,3,4,5,6].
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