Local entrapment of interferon γ in the recovery from Shigella dysenteriae type 1 infection

Abstract

In healthy controls (n = 8) living in shigella endemic areas, accumulation of interferon gamma (IFN γ) in the epithelial lining was seen in the rectal tissues. At the single cell level, however, few or no IFN γ protein producing cells or mRNA expressing cells were detected at that site indicating the involvement of the whole large intestine in the production of IFN γ in controls. Persistent numbers of IFN γ producing cells were detected in the rectum of patients with Shigella dysenteriae type 1 infection (n = 8) throughout the course of disease with a tendency to increase in the convalescent stage. A significantly increased extra cellular deposition of secreted IFN γ in tissue was seen in convalescence when compared with the acute stage (p < 0.05). In addition, enzyme immunoassay showed increased stool concentration of IFN γ in patients at the convalescent stage as well as in healthy controls. In situ hybridisation confirmed the results by showing increased frequency of IFN γ mRNA containing cells at the late stage of the disease (p < 0.05). Extensive message for IFN γ was evident in cells in the lamina propria with no detectable transcripts in the surface epithelium. A colocalisation of IFN γ with the IFN γ receptor expression, predominantly found in the epithelial lining was detected by immunohistochemistry. Semiquantitative evaluation by computerised image analysis showed a gradual increased expression of IFN γ and its corresponding receptor in the convalescent stage of shigellosis. This suggested progressive entrapment and binding of IFN γ to its specific receptor at the local site. The enhanced surface expression of IFN γ receptor evident at the convalescent stage of shigellosis was comparable to the constitutive level of expression in the healthy subjects. Thus, immunity to shigellosis correlated to up-regulation of IFN γ production and expression of IFN γ receptor.