Dr. Gaëlle Lentini

We investigate the intricate molecular interactions between intracellular pathogens and their host cells, focusing on how these dynamics drive cellular responses that contribute to pathogenesis.

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Chronic infection with the intracellular parasite Trypanosoma cruzi drives the development of Chagas disease in humans, leading to severe cardiac, digestive, or neurological complications. T. cruzi has a significant global health impact, affecting millions of people—primarily in Latin America, but increasingly worldwide due to migration. The disease often remains undiagnosed in its early stages and can progress into chronic infection. Current treatments are limited, with variable efficacy depending on the stage of the disease, and no vaccines are currently available. Advancing research on T. cruzi is a formidable yet essential endeavor, critical to addressing this neglected tropical disease and improving the lives of millions.

In our team, we investigate the biology of Trypanosoma cruzi, focusing on the parasite's interactions with host cells that drive its dissemination, survival, and persistence.

THEME: “EGRESS”

During the acute and chronic phase of the infection, effective and timely regulated parasite egress is crucial for the parasite survival, dissemination and persistence. Despite its importance in disease progression, the molecular mechanisms of active T. cruzi exit from its host cell are unknown.

  • What is the dynamic of the host cytoskeleton during infection?

Intracellular T. cruzi resides free in the host cell cytoplasm and depends on host metabolic resources and host organelles interaction for its growth. During infection, an extensive remodelling of the host cytoskeleton has been observed. This peculiar cytoskeletal arrangement, driven by the infection, suddenly break down right before host cell lysis and egress of the parasite.

We aim to study the dynamic of different cytoskeletal elements before and during the egress process to understand which structures T. cruzi destabilizes to facilitate its exit from the host cell.

Micropatterns used to dictate cytoskletal arrangement in infected cells
Micropatterns used to dictate cytoskletal arrangement in infected cells
  • Which are the molecular players of active host cell exit?

During decades, T. cruzi exit has been attributed to the extensive parasite motility, thought to be sufficient to induce mechanical rupture of the host cell membrane. However, recent work has revealed that T. cruzi egress is an event driven by the parasite. As for many intracellular pathogens, the timing and mechanisms underlying T. cruzi egress are temporally controlled and very much parasite specific. By combining genetic manipulation and cutting-edge mass spectrometry technologies, we aim to identify and functionally characterized the molecular players driving the sudden host cell lysis and parasite release in T. cruzi.

THEME: “CELLULAR TRANSFORMATION”

During its life cycle in a mammalian host, T. cruzi alternates between its infective form, the trypomastigote, and its replicative form, the amastigote. Upon host cell invasion, trypomastigotes undergo drastic morphological and molecular changes to transform into amastigotes, initiating replication within their intracellular niche. At the end of the lytic cycle, intracellular amastigotes transition back to the infective trypomastigote form, in a semi-concerted manner. This process leaves the host cell filled with motile, infectious trypomastigotes, which are then released upon egress, to initiate a new lytic cycle.

This transformation, known as trypomastigogenesis, is a pivotal step in the parasite's life cycle, enabling it to spread within the host and sustain infection. It involves profound changes in the parasite's structure and function to adapt to its role as an infectious agent.

Leveraging Ultra-Expansion Microscopy (U-ExM), transgenic reporter strains, and genetic tools, we investigate the cellular structural reorganizations and molecular pathways driving the transition from replicative to infective forms. This work aims to uncover pathways that govern changes in cell shape, structure, and function. Such stage transitions are widely observed in other eukaryotic cells, and understanding these processes can illuminate the evolutionary and molecular mechanisms behind stage-specific adaptations.

ultra expension microscopy in infected host cell
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