The T. gondii tachyzoite, a biological model incredibly adapted for fast motion

 

Accounting for initiation of tissue acute damages is the striking ability of tachyzoite to invade about any metazoan nucleated cells. Once enclosed in a peculiar compartment, the tachyzoite multiplies until the former fills most of the host cell cytoplasm:  the progeny actively exits prior invading other cells, thus amplifying locally or more distantly the parasitic process in the hosts.

Tachyzoites are several micron-sized ellipsoid polarized cells that glide on substrates at speeds of several microns per second, an order of magnitude faster that the fastest human cells. They also penetrate into their target cells within a few tens of seconds in sharp contrast with the minute-scale of macropinocytosis/phagocytosis used by many other intracellular microbes.

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Our lab is primarily interested in decoding tachyzoite motility and cell invasive skills. We want to:

 

RESEARCH THEME 1

- Achieve a comprehensive dynamic model of how the tachyzoite generates force(s) to move towards and invades target cells under 2D and 3D microenvironments.

 

RESEARCH THEME 2

- Provide nanoscale structural and functional characterization of the “RON invasive nanodevice” prior and upon injection into the target cell membrane/cortex, a device key to initiate and support active invasion.

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In the same line, we are interested in understanding how a tachyzoite subpopulation reaches and colonizes the so-called priviledged tissues in which T. gondii switches to the slow replicative developmental and persistent stage.

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RESEARCH THEME 3

- Decipher how much tachyzoites depend on their own motile skills or/and on host leucocytic « shuttles » to (i) avoid immune killing during the acute phase of parasitism following ingestion of contaminated stages and (ii) sustain parasite dissemination through the host tissues/vasculatures.

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Our basic and trans-disciplinary research programs lie at the interface between parasitology, cell biology and biophysics and require the development of nano-tools and technologies provided through the tight collaboration with physicists (in priority from the LIPhy, Grenoble). The Toxoplasma parasite is not only seen as a widely spread infectious and « potential killer » microbe but also as a fascinating probe unveiling fundamental regulatory mechanisms of cell and tissue homeostasis under constant challenge during asymptomatic and symptomatic phases of parasitism*.

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*In the context of the interdisciplinary spirit of our research, continuous feedback with the neighbor team of Mohamed-Ali Hakimi "Host-pathogen interactions & Immunity to infections" and with the I. Tardieux mentor, Geneviève Milon (Institute Pasteur Paris, Dr Emerit) ground progress in our day after day research.

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Key recent Achievements of the team

 

• The T. gondii tachyzoite applies traction force at the Zoite Cell Jonction - (Bichet et al., BMC Biology, 2014),

• The mammalian actin nucleator Spire-1 contributes to the invadosome in cancer cells and its associated invasive properties. Lagal et al., J Cell Sci., 2014),

• AMA1-deficient T. gondii parasites can still establish in vitro and in vivo infection - (Lagal et al., Infection and Immunity, 2015),

• Motor-deficient T. gondii tachyzoites use an alternative mode of entry in the host cell - (Bichet et al., BMC Biology, 2016),

• A specific twisting motion of the parasite terminates entry into a PV -  (Pavlou et al., Cell Host Microbe, 2018)