Shigella impairs T lymphocyte dynamics in vivo

Abstract

The Gram-negative enteroinvasive bacterium Shigella flexneri is responsible for the endemic form of bacillary dysentery, an acute rectocolitis in humans. S. flexneri uses a type III secretion system to inject effector proteins into host cells, thus diverting cellular functions to its own benefit. Protective immunity to reinfection requires several rounds of infection to be elicited and is short-lasting, suggesting that S. flexneri interferes with the priming of specific immunity. Considering the key role played by T-lymphocyte trafficking in priming of adaptive immunity, we investigated the impact of S. flexneri on T-cell dynamics in vivo. By using two-photon microscopy to visualize bacterium-T-cell cross-talks in the lymph nodes, where the adaptive immunity is initiated, we provide evidence that S. flexneri, via its type III secretion system, impairs the migration pattern of CD4 + T cells independently of cognate recognition of bacterial antigens. We show that bacterial invasion of CD4 + T lymphocytes occurs in vivo, and results in cell migration arrest. In the absence of invasion, CD4+ T-cell migration parameters are also dramatically altered. Signals resulting from S. flexneri interactions with subcapsular sinus macrophages and dendritic cells, and recruitment of polymorphonuclear cells are likely to contribute to this phenomenon. These findings indicate that S. flexneri targets T lymphocytes in vivo and highlight the role of type III effector secretion in modulating host adaptive immune responses.host-pathogen cross-talks | imaging

How Do the Virulence Factors of Shigella Work Together to Cause Disease?

“…Cells transfected with IpgD-GFP and incubated with CXCL12 had no ERM protein localization at the pole, preventing T-cell polarization and migration (Konradt et al, 2011). Mean velocity of T-cells was measured in vivo , with uninfected T-cells exhibiting 9 and 4 μm/min for wild-type Shigella -infected T-cells (Salgado-Pabón et al, 2013). This indicates that Shigella is capable of affecting T-cells in the context of infection, and that this ability is dependent on IpgD.…”

Actin polymerization as a key innate immune effector mechanism to control Salmonella infection

“…Inflammasome-induced cellular stiffening and arrest may represent a general mechanism for the control of intracellular bacterial infection. Earlier work showed that CD4 + T lymphocytes infected with Shigella flexneri exhibit an impaired ability to migrate in vitro and in vivo (34,35). Shigella can drive inflammasome activation through both NLRC4 and NLRP3 (36,37), but it remains to be determined whether increased cell stiffness and impaired movement in immune cells are a consequence of inflammasome activity induced by pathogens other than Salmonella, such as Shigella or Listeria.…”

Injection of T3SS effectors not resulting in invasion is the main targeting mechanism of Shigella toward human lymphocytes

“…To understand why several rounds of Shigella infection induce only a short-term protective humoral immunity and thus overcome the challenges of vaccine development (3,4), a better knowledge of Shigella-immune cell interactions is necessary. Over the last years, Shigella has been shown to not only target innate immune cells (5) but also to directly impact adaptive immune cells through mechanisms dependent upon its T3SS (6)(7)(8). Our previous studies of Shigella-lymphocytes cross talks suggested that, besides invasion of these cells, injection of Shigella T3SS effectors not resulting in invasion might also occur (6).…”