iiinova — where your digital self keeps evolving

Bryan Bryson

@thebrysonlab.bsky.social

1.8K followers 1.3K following 63 posts

Tuberculosis, systems immunology, innate immunity, vaccines, computational biology. www.brysonlab.org

Posts Replies Media

Bryan Bryson @thebrysonlab.bsky.social · 20/11/2025

2. For those of you who know Mtb, you'll know that Mtb mutants lacking the virulence lipid, PDIM, partially phenocopy ESX-1 mutants. We asked if PDIM mutants have a similar MHC-I phenotype. They didn't! This argues there is a specific role for the ESX-1 secretion system in MHC-I presentation

110

Bryan Bryson @thebrysonlab.bsky.social · 20/11/2025

So, we were stuck. Our data point to a role for ESX-1 in presentation but was it the secretion system or some other response that is downstream of ESX-1? So we did 2 experiments 1. We did discovery MS with macrophages infected with an ESX-1 mutant and asked if we could see Mtb-derived peptides. No!

110

Bryan Bryson @thebrysonlab.bsky.social · 20/11/2025

We examined the role of newly identified host pore-forming proteins (MPEG-1) to define their role in presentation of Mtb-derived peptides, and they were dispensable.

110

Bryan Bryson @thebrysonlab.bsky.social · 20/11/2025

OK, so ESX-1 controls galectin recruitment to the phagosome. Can we figure out a way to restore galectin positivity to the phagosome of an ESX-1 mutant? Yes, we used some previously identified small molecules and restored galectin positivity, but it did not rescue presentation.

110

Bryan Bryson @thebrysonlab.bsky.social · 20/11/2025

We first tested an antigen expression hypothesis -- is the loss of presentation of Mtb-derived peptides on MHC-I explained by loss of expression of these antigens in the ESX-1 mutant in macrophages? No! If anything, we see elevated gene expression in the mutant.

110

Bryan Bryson @thebrysonlab.bsky.social · 20/11/2025

In our previous paper, we showed that loss of ESX-1 disrupts presentation of Mtb-derived peptides on MHC-I using immunopeptidomics. Here, we first corroborated those findings using a T cell clone specific for one of the peptides we saw by MS.

Bar graph showing CD69 positivity on an EsxJ-specific T cell clone following co-culture with macrophages (mock infected, WT infected, ESX-1 mutant infected).

120

Bryan Bryson @thebrysonlab.bsky.social · 17/11/2025

So we took a step back and realized that in our hands human macrophages have more lipid droplets (LDs) at baseline than murine macrophages, so we tested the hypothesis that human LDs regulated the ability of Mtb to acquire and store lipids. Inhibition of host TAG synthesis did the trick (partially)!

Microscopy images of Mtb within human macrophages that have been treated with different inhibitors of TAG synthesis. White arrows point to where lipid inclusions become detectable in human macrophages.

110

Bryan Bryson @thebrysonlab.bsky.social · 17/11/2025

Many of these Mtb genes were associated with lipid metabolism, so we orthogonally validated these observations by tracking Mtb acquisition and storage of lipids using established techniques and found that Mtb readily forms intracellular lipid inclusions in mouse but not human macrophages

Microscopy images examining lipids in green, Mtb and nuclei. The image looks at Mtb in human or mouse macrophages using two different lipid probes.

111

Bryan Bryson @thebrysonlab.bsky.social · 17/11/2025

Here in work led by postdoc Jonathan Padilla-Gomez, we asked that question using an vitro model of Mtb infection of either primary human or mouse macrophages. To our surprise, we found many differentially expressed Mtb genes across host environments

Volcano plot examining the log2 fold change and adjusted p value of Mtb gene expression between human and mouse macrophages.

100

Bryan Bryson @thebrysonlab.bsky.social · 25/09/2025

Congrats to the Carpenter Lab on this exciting study! I might now sound like a broken record, but check the abstract!!! Let’s go type 7 secretion system substrates! #tuberculosis #tbsky

060

Bryan Bryson @thebrysonlab.bsky.social · 21/07/2025

Importantly, for Mtb, the results are consistent with our previous study (doi.org/10.7554/eLif...) where we showed that Mtb-derived peptides on MHC-I are enriched for type VII secretion system substrates underscoring our enthusiasm for including these antigens in TB vaccines.

150

Bryan Bryson @thebrysonlab.bsky.social · 05/05/2025

Pictured: glass of champagne I treated myself to at DCA upon learning the lab has been tenured! Grateful to my lab family, my extended science family, and my family for the amazing support and love offered on the journey so far. Much more work left to do but taking this moment to say thank you!

24723

Bryan Bryson @thebrysonlab.bsky.social · 06/12/2024

A lovely day to celebrate the amazing people I work with every day

1172