Thanks Igor! 😊
Thank you so much!! 😊
Thrilled that our latest paper showing that DCs undergo either pyroptosis or apoptosis upon bacterial blockade of host translation to restrict Legionella is now online at the @asm.org journal mBio! Congrats to 1st author @vvazquez.bsky.social & co-authors! 🎉 journals.asm.org/doi/10.1128/...
Excited to share that our paper examining how GM-CSF potentiates cytokine responses in human monocytes during bacterial infection is now online at the @asm.org journal Infection & Immunity! Congrats to @vvazquez.bsky.social, @mikelhaggadone.bsky.social, & co-authors! journals.asm.org/doi/full/10....
Thank you Sunny for all your support!! I wouldn’t have made it this far without your mentorship. I am truly grateful to have learned from you how to be a scientist and contribute to the community. I’m excited to continue my journey in the Monack lab with all the knowledge i gained in your lab ❤️
Thank you!! 😊
I would also like to thank @brodskyigorlab.bsky.social for his feedback as well as his lab for providing reagents. And finally, thank you to whoever is reading this thread :) (14/14)
Thank you to my lab peers Kimmie Wodzanowski and Jenna Zhang for helping with experiments. I want to thank my undergrad and graduate mentees that made important contributions to this work: Allyson Lu, Frankie Boyer, Isabel Vargas, Suzana Hossain, Karly Kammann, and Madison Dresler. (13/14)
First, a huge thank you to @sunnyshinlab.bsky.social for being the most amazing mentor anyone could have asked for. Thank you to our former postdoc Jess Doerner for starting this project and teaching me the tools to further develop it. (12/14)
We have many exciting unanswered questions that we will be exploring in the future! This work was a huge collaborative effort, and I am grateful to have worked with so many amazing scientists. (11/14)
We think that DCs are more sensitive than macrophages due to lower basal expression of anti-apoptotic proteins. This work will serve as foundation for understanding whether other bacterial pathogens similarly activate these pathways in DCs and other cell types. (10/14)
Collectively, we show that DCs restrict Legionella by activating pyroptosis and effector-triggered apoptosis. Our findings suggest Mcl-1 and cFLIP guard host protein synthesis and detect bacterial translation inhibition in DCs. (9/14)
Finally, effector-triggered apoptosis restricted Legionella replication to a greater extent than pyroptosis, but both were required for maximal restriction of Legionella by DCs. (8/14)
At the single-cell level, infected DCs do not simultaneously undergo pyroptosis and apoptosis, but rather exhibit heterogeneity. We found that one DC population underwent rapid pyroptosis, whereas at later timepoints another group of DCs activated effector-triggered apoptosis. (7/14)
We found that DCs also activate caspase-11-dependent pyroptosis. Our kinetic cell death assays revealed that DCs activate pyroptosis first followed by effector-triggered apoptosis, and that both of these pathways account for the majority of the programmed death occurring in DCs. (6/14)
However, when we looked at cell death kinetically, we found that effector-triggered apoptosis did not account for all of the DC death. This led us to interrogate whether DCs also activate pyroptosis in response to Legionella. (5/14)
These effectors downregulate anti-apoptotic factors Mcl-1 and cFLIP. We propose that these proteins guard host protein synthesis and that their depletion triggers apoptosis. (4/14)
Protein synthesis inhibitors can trigger apoptosis by depleting anti-apoptotic proteins. Legionella has seven T4SS effectors that block translation, and we found they cause DC apoptosis. (3/14)
Legionella injects effectors via its type IV secretion system (T4SS) to robustly replicate in macrophages. In contrast, Legionella T4SS activity triggers rapid DC apoptosis, restricting bacterial replication. We wanted to elucidate the host and bacterial factors involved in this DC response. (2/14)
Innate immune cells detect pathogens through PAMPs and bacterial effector activities, the latter triggering effector-triggered immunity or guard immunity. I aimed to identify which ETI pathways different cell types use and what effector activities trigger them, using Legionella as a model (1/14)
Bluesky post
I’m very excited to share a preprint of the bulk of my thesis work in @sunnyshinlab.bsky.social where we investigate how dendritic cells respond to Legionella pneumophila
www.biorxiv.org/content/10.1...
I would also like to thank @brodskyigorlab.bsky.social for his feedback as well as his lab for providing reagents. And finally, thank you to whoever is reading this thread :) (14/14)
Thank you to my lab peers Kimmie Wodzanowski and Jenna Zhang for helping with experiments. I want to thank my undergrad and graduate mentees that made important contributions to this work: Allyson Lu, Frankie Boyer, Isabel Vargas, Suzana Hossain, Karly Kammann, and Madison Dresler. (13/14)
First, a huge thank you to @sunnyshinlab.bsky.social for being the most amazing mentor anyone could have asked for. Thank you to our former postdoc Jess Doerner for starting this project and teaching me the tools to further develop it. (12/14)
We have many exciting unanswered questions that we will be exploring in the future! This work was a huge collaborative effort, and I am grateful to have worked with so many amazing scientists. (11/14)
We think that DCs are more sensitive than macrophages due to lower basal expression of anti-apoptotic proteins. This work will serve as foundation for understanding whether other bacterial pathogens similarly activate these pathways in DCs and other cell types. (10/14)
Collectively, we show that DCs restrict Legionella by activating pyroptosis and effector-triggered apoptosis. Our findings suggest Mcl-1 and cFLIP guard host protein synthesis and detect bacterial translation inhibition in DCs. (9/14)
Finally, effector-triggered apoptosis restricted Legionella replication to a greater extent than pyroptosis, but both were required for maximal restriction of Legionella by DCs. (8/14)
At the single-cell level, infected DCs do not simultaneously undergo pyroptosis and apoptosis, but rather exhibit heterogeneity. We found that one DC population underwent rapid pyroptosis, whereas at later timepoints another group of DCs activated effector-triggered apoptosis. (7/14)
We found that DCs also activate caspase-11-dependent pyroptosis. Our kinetic cell death assays revealed that DCs activate pyroptosis first followed by effector-triggered apoptosis, and that both of these pathways account for the majority of the programmed death occurring in DCs. (6/14)
