About

Professor Bryan Bryson is the Phillip and Susan Ragon Career Development Professor at MIT's Department of Biological Engineering. His research focuses on engineering the host-pathogen interface, with the ultimate goal of manipulating the immune system to improve bacterial control. Combining new technologies with classical approaches, his work aims to develop solutions for infectious diseases, particularly tuberculosis. Bryson's research involves dissecting the complex dynamics of bacterial infection at various scales, from single cells to infected animals, using both immunological and microbiological perspectives. Bryson obtained his undergraduate degree in mechanical engineering and a PhD in biological engineering at MIT. He then pursued postdoctoral training with Sarah Fortune at the Harvard School of Public Health, where he developed an interest in leveraging modern biological engineering approaches to understand tuberculosis pathogenesis. His lab is dedicated to understanding how to manipulate the immune response to better control bacterial infections, with recent advances contributing to the development of new tools and potential vaccines, including efforts related to tuberculosis and the BCG vaccine.

Research topics

• Biology
• Computer Science
• Genetics
• Natural Language Processing
• Medicine
• Immunology
• Philosophy
• Programming language
• Linguistics
• Biochemistry
• Microbiology
• Pathology
• Virology

Selected publications

• eLife Assessment: Reprogramming of host energy metabolism mediated by the TNF-iNOS-HIF-1α axis plays a key role in host resistance to Plasmodium infection

  2026-03-12

  peer-reviewOpen access1st authorCorresponding

  TNF has a dual effect in Plasmodium infection, bolstering the host’s immune defense while also inducing sickness behavior. Here, we show that TNF signaling hampers physical activity, food intake, and energy expenditure while enhancing glucose uptake by the liver and spleen as well as controlling parasitemia in P. chabaudi (Pc)-infected mice. We also report that TNF is required for expression of inducible nitric oxide synthase (iNOS), stabilization of HIF-1α, expression of glucose transporter GLUT1 and enhanced glycolysis in monocytic cells from Pc-infected mice. Importantly, Pc-infected iNOS-/-, TNFRΔLyz2 and HIF-1αΔLyz2 mice show impaired release of TNF and glycolysis in monocytes, along with increased parasitemia and disease tolerance. Altogether, our results indicate that TNF-iNOS-HIF-1α-induced glycolysis in monocytes plays a critical role in host defense and sickness behavior in Pc-infected mice.

  PublisherDOI

• Neutrophils repurpose the nucleolus as a cytokine reservoir and secretory organelle

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-20

  article

  Type I interferons (IFN-I) are critical for antiviral defense but can drive severe pathology when dysregulated. Excess IFN-I is associated with prominent neutrophil accumulation; however, the contribution of neutrophils to IFN-I overproduction remains underexplored. In all cell types previously studied, IFN-I is synthesized de novo following sensing of microbial or host-derived inflammatory stimuli. Contrary to this paradigm, we find that neutrophils express IFNα during development and store it in the nucleolus, a membrane-less intranuclear condensate classically functioning in ribosome biogenesis. TLR-mediated bacterial sensing induces a nucleolar stress response in neutrophils that triggers rapid release of nucleoli-stored IFNα independent of de novo protein synthesis. These findings reveal that neutrophils have repurposed the nucleolus as a cytokine storage and secretory organelle, identify the first naturally occurring immunoregulatory function of nucleolar stress, and provide insight into the relationship between detrimental IFN-I levels and neutrophil accumulation.

  PublisherDOI

• eLife Assessment: High-throughput neutralization measurements correlate strongly with evolutionary success of human influenza strains

  2025-06-03

  peer-reviewOpen access1st authorCorresponding

  Human influenza viruses rapidly acquire mutations in their hemagglutinin (HA) protein that erode neutralization by antibodies from prior exposures. Here, we use a sequencing-based assay to measure neutralization titers for 78 recent H3N2 HA strains against a large set of children and adult sera, measuring ∼10,000 total titers. There is substantial person-to-person heterogeneity in the titers against different viral strains, both within and across age cohorts. The growth rates of H3N2 strains in the human population in 2023 are highly correlated with the fraction of sera with low titers against each strain. Notably, strain growth rates are less correlated with neutralization titers against pools of human sera, demonstrating the importance of population heterogeneity in shaping viral evolution. Overall, these results suggest that high-throughput neutralization measurements of human sera against many different viral strains can help explain the evolution of human influenza.

  PublisherDOI

• eLife Assessment: Synaptotagmin 1 and Synaptotagmin 7 promote MR1-mediated presentation of Mycobacterium tuberculosis antigens

  2025-09-24

  peer-reviewOpen access1st authorCorresponding

  Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that can be sensed by T cells, which are essential for the control of infection. In comparison to viral infections, Mtb antigens are relatively rare and hence, challenging to sample. Specialized antigen presentation pathways enable the presentation of such scarce antigens to CD8+ T cells, which are, thus, uniquely poised to survey intracellular environments. A subset of CD8+ T cells prevalent in the airways, known as mucosal associated invariant T (MAIT) cells, can be activated through the presentation of Mtb antigens via the MHC class I-related protein 1 (MR1) molecule. Prior work demonstrates that endosomal calcium signaling is critical for MR1-mediated presentation of Mtb-derived antigens. Here, we show that the calcium-sensing trafficking proteins Synaptotagmin (Syt) 1 and Syt7 specifically promote MAIT cell activation in response to Mtb-infected cells. In bronchial epithelial cells, Syt1 and Syt7 localize to late endo-lysosomes and MR1 vesicles. Loss of Syt1 and Syt7 results in enlarged MR1 vesicles and an increased number of MR1 vesicles in close proximity to Mtb-containing vacuoles during infection. This study identifies a novel pathway in which Syt1 and Syt7 facilitate the translocation of MR1 from Mtb-containing vacuoles, potentially to the cell surface for antigen presentation.

  PublisherDOI

• Targeting infection-specific peptides in immunopeptidomics studies for vaccine target discovery

  The Journal of Experimental Medicine · 2025-07-01 · 6 citations

  article

  Vaccine-elicited T cell responses can contribute to immune protection against emerging infectious disease risks such as antimicrobial-resistant (AMR) microbial pathogens and viruses with pandemic potential, but rapidly identifying appropriate targets for T cell priming vaccines remains challenging. Mass spectrometry (MS) analysis of peptides presented on MHCs can identify potential targets for protective T cell responses in a proteome-wide manner. However, pathogen-derived peptides are outnumbered by self-peptides in the MHC repertoire and may be missed in untargeted MS analyses. Here, we present a novel approach, termed PathMHC, that uses computational analysis of untargeted MS data followed by targeted MS to discover novel pathogen-derived MHC peptides more efficiently than untargeted methods alone. We applied this workflow to identify MHC peptides derived from multiple microbes, including potential vaccine targets presented on MHC-I by human dendritic cells infected with Mycobacterium tuberculosis (Mtb), finding that all Mtb peptides detected in the MHC-I repertoire derived from proteins exported by type VII secretion systems. PathMHC will facilitate antigen discovery campaigns for vaccine development.

  PublisherDOI

• eLife Assessment: Single-cell profiling of the lung immune cells of diabetes-tuberculosis comorbidity reveals reduced type-II interferon and elevated Th17 responses

  2025-05-21

  peer-reviewOpen access1st authorCorresponding

  Understanding the perturbed lung immune cells distribution and its functionality in tuberculosis (TB) is well documented; however, limited reports have covered their disruption, if any, in diabetes-tuberculosis (DM-TB) comorbid conditions. Here, we employed single-cell RNA-seq to investigate the molecular mechanisms that govern the heterogeneity in host immune response in DM-TB comorbid conditions. Diabetes is associated with chronic hyperinflammation and reduced lung-infiltrating immune cells, which delays the immune response to Mycobacterial infection. scRNA-seq of lung CD3⁺ and CD11c⁺ cells revealed compromised adaptive and innate immunity, with decreased Th1 and M1 macrophage populations in DM-TB mice. A dampened immune response, marked by increased IL-16 signaling and reduced TNF and IFN-II responses, was observed in DM-TB. This study highlights chronic inflammation, hyperglycemia, and dyslipidemia associated with diabetes impairing anti-TB immunity. Selective inhibition of aberrant IL-16 secretion and Th17 cell activation might provide strategies for better managing DM-TB comorbidity.

  PublisherDOI

• IFN-γ- GranzymeB + Natural killer cells are induced by IV BCG vaccination and associated with protection against tuberculosis in rhesus macaques

  Mucosal Immunology · 2025-11-01 · 1 citations

  article
  PublisherDOI

• Antibody-Fab and -Fc features promote Mycobacterium tuberculosis restriction

  Immunity · 2025-05-30 · 9 citations

  articleOpen access

  Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), a leading cause of death by an infectious disease globally, has no efficacious vaccine. Antibodies are implicated in M. tuberculosis control, but the mechanisms of action remain poorly understood. We assembled a library of monoclonal antibodies (mAb) and screened for M. tuberculosis-restrictive activity in mice, identifying protective antibodies targeting diverse antigens. To dissect the mechanism of mAb-mediated M. tuberculosis restriction, we optimized a protective lipoarabinomannan-specific mAb, generating Fc variants. In vivo analysis of these Fc variants revealed a role for Fc-effector function in M. tuberculosis restriction. Restrictive Fc variants altered distribution of M. tuberculosis across innate immune cells. Single-cell transcriptomics highlighted distinctly activated pathways within innate immune cell subpopulations, identifying early activation of neutrophils as a key signature of mAb-mediated M. tuberculosis restriction. Therefore, antibody-mediated restriction of M. tuberculosis is associated with reorganization of the tissue-level immune response to infection and depends on the collaboration of antibody Fab and Fc.

  PublisherDOI

• High-dose intravenous BCG vaccination induces enhanced immune signaling in the airways

  Science Advances · 2025-01-01 · 20 citations

  articleOpen accessSenior authorCorresponding

  Intradermal Bacillus Calmette-Guérin (BCG) is the most widely administered vaccine, but it does not sufficiently protect adults against pulmonary tuberculosis. Recent studies in nonhuman primates show that intravenous BCG administration offers superior protection against Mycobacterium tuberculosis ( Mtb ). We used single-cell analysis of bronchoalveolar lavage cells from rhesus macaques vaccinated via different routes and doses of BCG to identify alterations in the immune ecosystem in the airway following vaccination. Our findings reveal that high-dose intravenous BCG induces an influx of polyfunctional T cells and macrophages in the airways, with alveolar macrophages from high-dose intravenous BCG displaying a basal activation state in the absence of purified protein derivative stimulation, defined in part by interferon signaling. Enhanced intercellular immune signaling and stronger T helper 1–T helper 17 transcriptional responses were observed following purified protein derivative stimulation. These results suggest that high-dose intravenous BCG vaccination creates a specialized immune environment that primes airway cells for effective Mtb clearance.

  PublisherDOI

• Correction: Immunopeptidomics reveals determinants of Mycobacterium tuberculosis antigen presentation on MHC class I

  eLife · 2025-08-20

  erratumOpen accessSenior author
  PublisherDOI

Frequent coauthors

• Joshua M. Peters

  Ragon Institute of MGH, MIT and Harvard

  70 shared

• Alex K. Shalek

  Ragon Institute of MGH, MIT and Harvard

  63 shared

• Sarah M. Fortune

  53 shared

• Brian Hie

  Stanford University

  43 shared

• Owen Leddy

  Massachusetts Institute of Technology

  39 shared

• Bonnie Berger

  Massachusetts Institute of Technology

  38 shared

• Travis K. Hughes

  37 shared

• Forest M. White

  Massachusetts Institute of Technology

  31 shared

Labs

• Bryan Bryson LabPI

Awards & honors

• Wishnok Prize