First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Thibault Rosazza is first author on ‘Dynamic imaging reveals surface exposure of virulent Leishmania amastigotes during pyroptosis of infected macrophages’, published in JCS. Thibault conducted the research described in this article while a master's student in Dr Gerald Spaeth's lab at Institut Pasteur, Unite de Parasitologie Moleculaire et Signalisation, and is now a rotation PhD student in the lab of Dr Gabriel Solberger at University of Dundee, investigating host–pathogen interactions, emphasizing innate immunity modulations.
How would you explain the main findings of your paper in lay terms?
Pathogenesis of cutaneous leishmaniasis is characterized by the development of long-lasting skin lesions often associated with inflammatory reactions. The mechanisms utilized by intracellular Leishmania to survive in this anti-microbial environment and to spread from one host cell to another remain elusive. In this study, we found that once the main host cell of this parasite, the macrophage, undergoes an inflammatory cell death called pyroptosis, Leishmania is exposed at the cell surface. By applying high-content microscopy analysis combined with electronic microscopy, we precisely observed and quantified this phenomenon. Pyroptosis is known as an inflammatory cell death often associated with pathogen clearance. We described that Leishmania parasites survive this cytotoxic inflammatory response and retain the ability to infect new macrophages. Our findings represent a first observation of Leishmania egress from dying macrophages, shedding important new light on potential mechanisms underlying parasite dissemination and persistent infection.
Were there any specific challenges associated with this project? If so, how did you overcome them?
One of the main challenges of this project was to determine if Leishmania amastigotes were still attached to their host cell during pyroptosis. It was particularly important to address this question because it could help us to understand potential mechanisms used by Leishmania amastigotes to spread from one cell to another. Indeed, if parasites remained attached to their pyroptotic macrophages, we can emit the hypothesis that newly recruited macrophages would phagocyte these pyroptotic cells containing Leishmania amastigotes without triggering an anti-microbial response. To investigate parasite localization during macrophage pyroptosis, we combined high-content live imaging and electron microscopy approaches, and observed that Leishmania amastigotes remained attached to their pyroptotic host cell via a defined attachment site of the parasite to the parasitophorous vacuole membrane of the macrophage.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
I will always remember the first visualization of Leishmania amastigotes egressing from pyroptotic macrophages. At that time, we were focusing our interest on macrophage inflammasome activation during Leishmania infection. To our surprise, we observed that some parasites were expelled from their host cell after NLRP3 inflammasome activation. Curiously, even 4 hours after pyroptosis induction, parasites remained associated with the dying cells. It is this first intriguing observation that opened the new investigation now published in this study.
Why did you choose Journal of Cell Science for your paper?
We chose Journal of Cell Science given the important role of this journal in reporting cutting-edge cell biological research. We report the first observation of Leishmania egress from pyroptotic macrophages and we thought that our finding may be of broad interest to the journal's readership.
What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?
I think it is because my previous supervisors always involved me in exciting and challenging research projects that I wanted to start a PhD and become a scientist, too. By being involved directly in international collaborations, I gained a lot of maturity and independence, which convinced me to pursue my career in science. I will always remember the kick-off meeting of this project we had in Shanghai a few years ago. I think this is one of the reasons why I am a PhD student now. I discovered a multicultural environment focussing on one main objective and it was really stimulating intellectually and personally.
What's next for you?
I recently started the Wellcome Trust PhD programme at the School of Life Science at Dundee University. I want to continue to explore and understand how our immune system reacts and evolves under infectious pressure. More precisely, how our innate immune system – which constitutes the first line of defence against pathogens – mediates inflammation in order to create a proper immune response in our body.
Tell us something interesting about yourself that wouldn't be on your CV
I think that the international collaborations I was involved in had an unexpected impact on my life. Especially the one in Korea. A that time, in parallel to my growing interest in host–pathogen interactions, I also developed an addiction to kimchi. Luckily for my microbiota, I now try to master the art of fermented cabbage during my spare time.
Thibault Rosazza's contact details: School of Life Science, University of Dundee, UK.