Article

The Shigella flexneri Type Three Secretion System Effector IpgD Inhibits T Cell Migration by Manipulating Host Phosphoinositide Metabolism

Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France.
Cell host & microbe (Impact Factor: 12.33). 04/2011; 9(4):263-72. DOI: 10.1016/j.chom.2011.03.010
Source: PubMed

ABSTRACT

Shigella, the Gram-negative enteroinvasive bacterium that causes shigellosis, relies on its type III secretion system (TTSS) and injected effectors to modulate host cell functions. However, consequences of the interaction between Shigella and lymphocytes have not been investigated. We show that Shigella invades activated human CD4(+) T lymphocytes. Invasion requires a functional TTSS and results in inhibition of chemokine-induced T cell migration, an effect mediated by the TTSS effector IpgD, a phosphoinositide 4-phosphatase. Remarkably, IpgD injection into bystander T cells can occur in the absence of cell invasion. Upon IpgD-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP(2)), the pool of PIP(2) at the plasma membrane is reduced, leading to dephosphorylation of the ERM proteins and their inability to relocalize at one T cell pole upon chemokine stimulus, likely affecting the formation of the polarized edge required for cell migration. These results reveal a bacterial TTSS effector-mediated strategy to impair T cell function.

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Available from: Andrea Puhar, Jan 07, 2014
    • "T cells are a key component of the adaptive immune system and are required for protective immunity against many bacterial pathogens45678910. Recent studies have shown that a number of bacterial pathogens, including Salmonella Typhimurium, can directly inhibit T cells11121314151617, providing insight into the types of strategies used by pathogenic bacteria to overcome pathways of the adaptive immune system. Salmonellae are a leading cause of morbidity and mortality in humans worldwide18192021. "
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    • "In epithelial cells, the depletion of PI(4,5)P 2 contributes to the actin dynamics notably by disrupting the connections between cortical actin and the plasma membrane, whereas the production of PI(5)P induces activation of the PI3-kinase/Akt pathway, thereby promoting host cell survival (Niebuhr et al., 2002; Pendaries et al., 2006; Ramel et al., 2011). Recent studies indicate that IpgD prevents T cell migration at the site of infection and blocks ATP release to attenuate inflammation, suggesting that it plays a role in evading the immune response (Konradt et al., 2011; Puhar et al., 2013). Whereas the entry process into epithelial cells is rather well established , the molecular mechanism of vacuolar rupture used by Shigella remains to be defined. "
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    • "In vitro studies have shown that Shigella triggers rapid DC pyroptosis and apoptosis (Edgeworth et al., 2002; Kim et al., 2008). We recently demonstrated that Shigella invades activated human CD4 + T cells in vitro and inhibits T cell migration toward a chemoattractant stimulus dependent on the virulence effector IpgD (Konradt et al., 2011). Additionally, Shigella impairs T cell dynamics in vivo within the site of adaptive immunity priming, i.e., the LN (Salgado-Pabón et al., 2013). "
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