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Updated: Aug 9, 2026
Epithelial Cell Infection Analyses with Shigella
Published on: February 9, 2024
ShiA abrogates the innate T-cell response to Shigella flexneri infection
Molly A Ingersoll1, Arturo Zychlinsky
1Max Planck Institute for Infection Biology, 21/22 Schumannstrasse, 10117 Berlin, Germany.
Abstract:
Shigella spp. are the causative agent of bacillary dysentery. Infection results in acute colonic injury due to the host inflammatory response. The mediators of the damage, infiltrating polymorphonuclear leukocytes (PMN), also resolve the infection. Shigella flexneri's virulence effectors are encoded on its large virulence plasmid and on pathogenicity islands in the chromosome. The SHI-2 pathogenicity island encodes the virulence factor ShiA, which down-regulates Shigella-induced inflammation. In the rabbit ileal loop model, infection with a shiA null strain (DeltashiA) induces a more severe inflammation than wild-type infection. Conversely, a Shigella strain that overexpresses ShiA (ShiA+) is less inflammatory than the wild-type strain. To determine the host responses modulated by ShiA, we performed infection studies using the mouse lung model, which recapitulates the phenotypes observed in the rabbit ileal loop model. Significantly, ShiA+ strain-infected mice cleared the bacteria and survived infection, while wild-type- and DeltashiA strain-infected mice could not clear the bacteria and ultimately died. Surprisingly, microarray analysis of infected lungs revealed the regulation of genes involved in innate T-cell responses to infection. Immunohistochemistry showed that wild-type- and DeltashiA strain-infected animals have greater numbers of PMN and T cells in their lungs over the course of infection than ShiA+ strain-infected animals. These results suggest that the T-cell innate response is suppressed by ShiA in Shigella infections.
Insights
Shigella flexneri uses the virulence factor ShiA to suppress the host's innate T-cell response, reducing inflammation and improving survival during infection. This finding highlights ShiA's role in modulating host immunity.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Shigella spp. cause bacillary dysentery, leading to acute colonic injury driven by host inflammatory responses.
- The virulence factor ShiA, encoded by the SHI-2 pathogenicity island, is known to down-regulate inflammation during Shigella infections.
- Previous studies in rabbit models indicated that ShiA modulates inflammation, with null strains causing more severe inflammation and overexpressing strains being less inflammatory.
Purpose of the Study:
- To investigate the host responses modulated by the Shigella virulence factor ShiA.
- To determine the role of ShiA in modulating innate T-cell responses during Shigella infection.
- To evaluate the impact of ShiA expression on host survival and bacterial clearance in a mouse model.
Main Methods:
- Infection studies were conducted using a mouse lung model, recapitulating phenotypes observed in rabbit ileal loop models.
- Microarray analysis was employed to identify host gene expression changes in infected lungs.
- Immunohistochemistry was used to quantify polymorphonuclear leukocytes (PMN) and T cells in lung tissues.
Main Results:
- Mice infected with a ShiA-overexpressing (ShiA+) strain cleared bacteria and survived, unlike those infected with wild-type or shiA null (DeltashiA) strains, which succumbed to infection.
- Microarray analysis revealed significant regulation of genes associated with innate T-cell responses in infected lungs.
- Immunohistochemistry showed reduced numbers of PMN and T cells in the lungs of ShiA+-infected mice compared to wild-type and DeltashiA-infected mice.
Conclusions:
- The virulence factor ShiA suppresses the innate T-cell response during Shigella infections.
- ShiA plays a critical role in modulating host immunity, leading to improved bacterial clearance and survival.
- Targeting ShiA-mediated immune suppression could offer novel therapeutic strategies for Shigella infections.
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