pubs.yml

- pubmed: https://pubmed.ncbi.nlm.nih.gov/38617225/
  key: 2024-sheridan-38617225
  title: A specific and portable gene expression program underlies antigen archiving
    by lymphatic endothelial cells
  pmid: PMID 38617225
  date: April 02, 2024
  year: '2024'
  authors:
  - Ryan Sheridan
  - Thu Doan
  - Cormac Lucas
  - Tadg Forward
  - Aspen Uecker-Martin
  - Thomas Morrison
  - Jay Hesselberth
  - Beth Tamburini
  abstract: Antigens from protein subunit vaccination traffic from the tissue to the
    draining lymph node, either passively via the lymph or carried by dendritic cells
    at the local injection site. Lymph node (LN) lymphatic endothelial cells (LEC)
    actively acquire and archive foreign antigens, and archived antigen can be released
    during subsequent inflammatory stimulus to improve immune responses. Here, we
    answer questions about how LECs achieve durable antigen archiving and whether
    there are transcriptional signatures associated with LECs containing high levels
    of antigen. We used single cell sequencing in dissociated LN tissue to quantify
    antigen levels in LEC and dendritic cell populations at multiple timepoints after
    immunization, and used machine learning to define a unique transcriptional program
    within archiving LECs that can predict LEC archiving capacity in independent data
    sets. Finally, we validated this modeling, showing we could predict antigen archiving
    from a transcriptional dataset of CHIKV infected mice and demonstrated in vivo
    the accuracy of our prediction. Collectively, our findings establish a unique
    transcriptional program in LECs that promotes antigen archiving that can be translated
    to other systems.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11014631/pdf/nihpp-2024.04.01.587647v1.pdf
  image: /images/2024-sheridan-38617225.jpg
  project:
  - project-1
  - project-2
  - project-3
  - core-c
- pubmed: https://pubmed.ncbi.nlm.nih.gov/33843587/
  links:
    github: https://github.com/rnabioco/antigen-tracking
    atlas: https://d3898ys7yh3545.cloudfront.net/
    geo: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150719
  project:
  - project-2
  - project-3
  - core-c
  fig_number: 7
  key: 2021-walsh-33843587
  title: Molecular tracking devices quantify antigen distribution and archiving in
    the murine lymph node
  pmid: PMID 33843587
  date: April 12, 2021
  year: '2021'
  authors:
  - Shannon Walsh
  - Ryan Sheridan
  - Erin Lucas
  - Thu Doan
  - Brian Ware
  - Johnathon Schafer
  - Rui Fu
  - Matthew Burchill
  - Jay Hesselberth
  - Beth Tamburini
  abstract: The detection of foreign antigens in vivo has relied on fluorescent conjugation
    or indirect read-outs such as antigen presentation. In our studies, we found that
    these widely used techniques had several technical limitations that have precluded
    a complete picture of antigen trafficking or retention across lymph node cell
    types. To address these limitations, we developed a 'molecular tracking device'
    to follow the distribution, acquisition, and retention of antigen in the lymph
    node. Utilizing an antigen conjugated to a nuclease-resistant DNA tag, acting
    as a combined antigen-adjuvant conjugate, and single-cell mRNA sequencing, we
    quantified antigen abundance in the lymph node. Variable antigen levels enabled
    the identification of caveolar endocytosis as a mechanism of antigen acquisition
    or retention in lymphatic endothelial cells. Thus, these molecular tracking devices
    enable new approaches to study dynamic tissue dissemination of antigen-adjuvant
    conjugates and identify new mechanisms of antigen acquisition and retention at
    cellular resolution in vivo.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116055/pdf/elife-62781.pdf
  image: /images/2021-walsh-33843587.jpg
- pubmed: https://pubmed.ncbi.nlm.nih.gov/29229919/
  project: project-2
  key: 2017-kedl-29229919
  title: Migratory dendritic cells acquire and present lymphatic endothelial cell-archived
    antigens during lymph node contraction
  pmid: PMID 29229919
  date: December 11, 2017
  year: '2017'
  authors:
  - Ross Kedl
  - Robin Lindsay
  - Jeffrey Finlon
  - Erin Lucas
  - Rachel Friedman
  - Beth Tamburini
  abstract: Antigens derived from viral infection or vaccination can persist within
    a host for many weeks after resolution of the infection or vaccine responses.
    We previously identified lymphatic endothelial cells (LEC) as the repository for
    this antigen archival, yet LECs are unable to present their archived antigens
    to CD8+ T cells, and instead transfer their antigens to CD11c+ antigen-presenting
    cells (APC). Here we show that the exchange of archived antigens between LECs
    and APCs is mediated by migratory dendritic cells (DC). After vaccination, both
    migratory basic leucine zipper ATF-like transcription factor 3 (BatF3)-dependent
    and BatF3-independent DCs are responsible for antigen exchange and cross-presentation.
    However, exchange of archived viral antigens is mediated only by BatF3-dependent
    migratory DCs potentially acquiring apoptotic LECs. In conclusion, LEC-archived
    antigens are exchanged with migratory DCs, both directly and through LEC apoptosis,
    to cross-present archived antigens to circulating T cells.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725486/pdf/41467_2017_Article_2247.pdf
  image: /images/2017-kedl-29229919.jpg
- pubmed: https://pubmed.ncbi.nlm.nih.gov/34618370/
  links:
    github: https://github.com/rnabioco/morrison-chikv
    geo: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE174667
    atlas: http://morrison-lnsc-browser.s3-website-us-east-1.amazonaws.com
  fig_number: 11
  project:
  - project-1
  - project-2
  - project-3
  - core-c
  key: 2021-carpentier-34618370
  title: MARCO+ lymphatic endothelial cells sequester arthritogenic alphaviruses to
    limit viremia and viral dissemination
  pmid: PMID 34618370
  date: November 15, 2021
  year: '2021'
  authors:
  - Kathryn Carpentier
  - Ryan Sheridan
  - Cormac Lucas
  - Bennett Davenport
  - Frances Li
  - Erin Lucas
  - Mary McCarthy
  - Glennys Reynoso
  - Nicholas May
  - Beth Tamburini
  - Jay Hesselberth
  - Heather Hickman
  - Thomas Morrison
  abstract: Viremia in the vertebrate host is a major determinant of arboviral reservoir
    competency, transmission efficiency, and disease severity. However, immune mechanisms
    that control arboviral viremia are poorly defined. Here, we identify critical
    roles for the scavenger receptor MARCO in controlling viremia during arthritogenic
    alphavirus infections in mice. Following subcutaneous inoculation, arthritogenic
    alphavirus particles drain via the lymph and are rapidly captured by MARCO+ lymphatic
    endothelial cells (LECs) in the draining lymph node (dLN), limiting viral spread
    to the bloodstream. Upon reaching the bloodstream, alphavirus particles are cleared
    from the circulation by MARCO-expressing Kupffer cells in the liver, limiting
    viremia and further viral dissemination. MARCO-mediated accumulation of alphavirus
    particles in the draining lymph node and liver is an important host defense mechanism
    as viremia and viral tissue burdens are elevated in MARCO-/- mice and disease
    is more severe. In contrast to prior studies implicating a key role for lymph
    node macrophages in limiting viral dissemination, these findings exemplify a previously
    unrecognized arbovirus-scavenging role for lymphatic endothelial cells and improve
    our mechanistic understanding of viremia control during arthritogenic alphavirus
    infection.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591538/pdf/EMBJ-40-e108966.pdf
  image: /images/2021-carpentier-34618370.jpg
- pubmed: https://pubmed.ncbi.nlm.nih.gov/35505125/
  project: project-2
  key: 2022-doan-35505125
  title: Trafficking and retention of protein antigens across systems and immune cell
    types
  pmid: PMID 35505125
  date: May 03, 2022
  year: '2022'
  authors:
  - Thu Doan
  - Tadg Forward
  - Beth Tamburini
  abstract: In response to infection or vaccination, the immune system initially responds
    non-specifically to the foreign insult (innate) and then develops a specific response
    to the foreign antigen (adaptive). The programming of the immune response is shaped
    by the dispersal and delivery of antigens. The antigen size, innate immune activation
    and location of the insult all determine how antigens are handled. In this review
    we outline which specific cell types are required for antigen trafficking, which
    processes require active compared to passive transport, the ability of specific
    cell types to retain antigens and the viruses (human immunodeficiency virus, influenza
    and Sendai virus, vesicular stomatitis virus, vaccinia virus) and pattern recognition
    receptor activation that can initiate antigen retention. Both where the protein
    antigen is localized and how long it remains are critically important in shaping
    protective immune responses. Therefore, understanding antigen trafficking and
    retention is necessary to understand the type and magnitude of the immune response
    and essential for the development of novel vaccine and therapeutic targets.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063628/pdf/18_2022_Article_4303.pdf
  image: /images/2022-doan-35505125.jpg
- pubmed: https://pubmed.ncbi.nlm.nih.gov/38194268/
  links:
    github: https://github.com/rnabioco/morrison-lnsc
    geo: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE243638
    atlas: http://morrison-lnsc-browser.s3-website-us-east-1.amazonaws.com
  project:
  - project-1
  - project-2
  - project-3
  - core-c
  key: 2024-lucas-38194268
  title: Chikungunya virus infection disrupts lymph node lymphatic endothelial cell
    composition and function via MARCO
  pmid: PMID 38194268
  date: January 09, 2024
  year: '2024'
  authors:
  - Cormac Lucas
  - Ryan Sheridan
  - Glennys Reynoso
  - Bennett Davenport
  - Mary McCarthy
  - Aspen Martin
  - Jay Hesselberth
  - Heather Hickman
  - Beth Tamburini
  - Thomas Morrison
  abstract: Infection with chikungunya virus (CHIKV) causes disruption of draining
    lymph node (dLN) organization, including paracortical relocalization of B cells,
    loss of the B cell-T cell border, and lymphocyte depletion that is associated
    with infiltration of the LN with inflammatory myeloid cells. Here, we find that
    during the first 24 h of infection, CHIKV RNA accumulates in MARCO-expressing
    lymphatic endothelial cells (LECs) in both the floor and medullary LN sinuses.
    The accumulation of viral RNA in the LN was associated with a switch to an antiviral
    and inflammatory gene expression program across LN stromal cells, and this inflammatory
    response, including recruitment of myeloid cells to the LN, was accelerated by
    CHIKV-MARCO interactions. As CHIKV infection progressed, both floor and medullary
    LECs diminished in number, suggesting further functional impairment of the LN
    by infection. Consistent with this idea, we find that antigen acquisition by LECs,
    a key function of LN LECs during infection and immunization, was reduced during
    pathogenic CHIKV infection.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143926/pdf/jciinsight-9-176537.pdf
  image: /images/2024-lucas-38194268.jpg
- pubmed: https://pubmed.ncbi.nlm.nih.gov/29997290/
  project:
  - project-1
  - project-2
  key: 2018-mccarthy-29997290
  title: Chikungunya virus impairs draining lymph node function by inhibiting HEV-mediated
    lymphocyte recruitment
  pmid: PMID 29997290
  date: July 12, 2018
  year: '2018'
  authors:
  - Mary McCarthy
  - Bennett Davenport
  - Glennys Reynoso
  - Erin Lucas
  - Nicholas May
  - Susan Elmore
  - Beth Tamburini
  - Heather Hickman
  - Thomas Morrison
  abstract: Chikungunya virus (CHIKV) causes acute and chronic rheumatologic disease.
    Pathogenic CHIKV strains persist in joints of immunocompetent mice, while the
    attenuated CHIKV strain 181/25 is cleared by adaptive immunity. We analyzed the
    draining lymph node (dLN) to define events in lymphoid tissue that may contribute
    to CHIKV persistence or clearance. Acute 181/25 infection resulted in dLN enlargement
    and germinal center (GC) formation, while the dLN of mice infected with pathogenic
    CHIKV became highly disorganized and depleted of lymphocytes. Using CHIKV strains
    encoding ovalbumin-specific TCR epitopes, we found that lymphocyte depletion was
    not due to impaired lymphocyte proliferation. Instead, the accumulation of naive
    lymphocytes transferred from the vasculature to the dLN was reduced, which was
    associated with fewer high endothelial venule cells and decreased CCL21 production.
    Following NP-OVA immunization, NP-specific GC B cells in the dLN were decreased
    during pathogenic, but not attenuated, CHIKV infection. Our data suggest that
    pathogenic, persistent strains of CHIKV disable the development of adaptive immune
    responses within the dLN.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124534/pdf/jciinsight-3-121100.pdf
  image: /images/2018-mccarthy-29997290.jpg
- pubmed: https://pubmed.ncbi.nlm.nih.gov/30045970/
  project:
  - project-1
  - project-2
  key: 2018-lucas-30045970
  title: Type 1 IFN and PD-L1 Coordinate Lymphatic Endothelial Cell Expansion and
    Contraction during an Inflammatory Immune Response
  pmid: PMID 30045970
  date: September 15, 2018
  year: '2018'
  authors:
  - Erin Lucas
  - Jeffrey Finlon
  - Matthew Burchill
  - Mary McCarthy
  - Thomas Morrison
  - Tonya Colpitts
  - Beth Tamburini
  abstract: Lymph node (LN) expansion during an immune response is a complex process
    that involves the relaxation of the fibroblastic network, germinal center formation,
    and lymphatic vessel growth. These processes require the stromal cell network
    of the LN to act deliberately to accommodate the influx of immune cells to the
    LN. The molecular drivers of these processes are not well understood. Therefore,
    we asked whether the immediate cytokines type 1 IFN produced during viral infection
    influence the lymphatic network of the LN in mice. We found that following an
    IFN-inducing stimulus such as viral infection or polyI:C, programmed cell death
    ligand 1 (PD-L1) expression is dynamically upregulated on lymphatic endothelial
    cells (LECs). We found that reception of type 1 IFN by LECs is important for the
    upregulation of PD-L1 of mouse and human LECs and the inhibition of LEC expansion
    in the LN. Expression of PD-L1 by LECs is also important for the regulation of
    LN expansion and contraction after an IFN-inducing stimulus. We demonstrate a
    direct role for both type 1 IFN and PD-L1 in inhibiting LEC division and in promoting
    LEC survival. Together, these data reveal a novel mechanism for the coordination
    of type 1 IFN and PD-L1 in manipulating LEC expansion and survival during an inflammatory
    immune response.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125167/pdf/nihms-981547.pdf
  image: /images/2018-lucas-30045970.jpg
- pubmed: https://pubmed.ncbi.nlm.nih.gov/31156626/
  project:
  - project-2
  - project-3
  - core-c
  links:
    geo: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE129933
  key: 2019-tamburini-31156626
  title: Chronic Liver Disease in Humans Causes Expansion and Differentiation of Liver
    Lymphatic Endothelial Cells
  pmid: PMID 31156626
  date: May 15, 2019
  year: '2019'
  authors:
  - Beth Tamburini
  - Jeffrey Finlon
  - Austin Gillen
  - Michael Kriss
  - Kent Riemondy
  - Rui Fu
  - Ronald Schuyler
  - Jay Hesselberth
  - Hugo Rosen
  - Matthew Burchill
  abstract: Liver lymphatic vessels support liver function by draining interstitial
    fluid, cholesterol, fat, and immune cells for surveillance in the liver draining
    lymph node. Chronic liver disease is associated with increased inflammation and
    immune cell infiltrate. However, it is currently unknown if or how lymphatic vessels
    respond to increased inflammation and immune cell infiltrate in the liver during
    chronic disease. Here we demonstrate that lymphatic vessel abundance increases
    in patients with chronic liver disease and is associated with areas of fibrosis
    and immune cell infiltration. Using single-cell mRNA sequencing and multi-spectral
    immunofluorescence analysis we identified liver lymphatic endothelial cells and
    found that chronic liver disease results in lymphatic endothelial cells (LECs)
    that are in active cell cycle with increased expression of CCL21. Additionally,
    we found that LECs from patients with NASH adopt a transcriptional program associated
    with increased IL13 signaling. Moreover, we found that oxidized low density lipoprotein,
    associated with NASH pathogenesis, induced the transcription and protein production
    of IL13 in LECs both in vitro and in a mouse model. Finally, we show that oxidized
    low density lipoprotein reduced the transcription of PROX1 and decreased lymphatic
    stability. Together these data indicate that LECs are active participants in the
    liver, expanding in an attempt to maintain tissue homeostasis. However, when inflammatory
    signals, such as oxidized low density lipoprotein are increased, as in NASH, lymphatic
    function declines and liver homeostasis is impeded.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530422/pdf/fimmu-10-01036.pdf
  image: /images/2019-tamburini-31156626.jpg
- pubmed: https://pubmed.ncbi.nlm.nih.gov/33053342/
  project:
  - project-2
  - core-b
  key: 2020-lucas-33053342
  title: PD-L1 Reverse Signaling in Dermal Dendritic Cells Promotes Dendritic Cell
    Migration Required for Skin Immunity
  pmid: PMID 33053342
  date: October 13, 2020
  year: '2020'
  authors:
  - Erin Lucas
  - Johnathon Schafer
  - Jennifer Matsuda
  - Madison Kraus
  - Matthew Burchill
  - Beth Tamburini
  abstract: Although the function of the extracellular region of programmed death
    ligand 1 (PD-L1) through its interactions with PD-1 on T cells is well studied,
    little is understood regarding the intracellular domain of PD-L1. Here, we outline
    a major role for PD-L1 intracellular signaling in the control of dendritic cell
    (DC) migration from the skin to the draining lymph node (dLN). Using a mutant
    mouse model, we identify a TSS signaling motif within the intracellular domain
    of PD-L1. The TSS motif proves critical for chemokine-mediated DC migration to
    the dLN during inflammation. This loss of DC migration, in the PD-L1 TSS mutant,
    leads to a significant decline in T cell priming when DC trafficking is required
    for antigen delivery to the dLN. Finally, the TSS motif is required for chemokine
    receptor signaling downstream of the Gα subunit of the heterotrimeric G protein
    complex, ERK phosphorylation, and actin polymerization in DCs.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688291/pdf/nihms-1638448.pdf
  image: /images/2020-lucas-33053342.jpg
- pubmed: https://pubmed.ncbi.nlm.nih.gov/37841845/
  project:
  - project-1
  - project-2
  - project-3
  - core-c
  key: 2023-tamburini-37841845
  title: Vaccine-induced antigen archiving enhances local memory CD8+ T cell responses
    following an unrelated viral infection
  pmid: PMID 37841845
  date: September 25, 2023
  year: '2023'
  authors:
  - Beth Tamburini
  - Thu Doan
  - Tadg Forward
  - Erin Lucas
  - Ira Fleming
  - Aspen Uecker-Martin
  - Jay Hesselberth
  - Thomas Morrison
  abstract: Viral and vaccine antigens persist or are archived in lymph node stromal
    cells (LNSC) such as lymphatic endothelial cells (LEC) and fibroblastic reticular
    cells (FRC). Here, we find that, during the time frame of antigen archiving, LEC
    apoptosis caused by a second, but unrelated, innate immune stimulus such as vaccina
    viral infection or CpG DNA administration boosted memory CD8+ T cells specific
    to the archived antigen. In contrast to "bystander" activation associated with
    unrelated infections, the memory CD8+ T cells specific to the vaccine archived
    antigen were significantly higher than memory CD8+ T cells of a different antigen
    specificity. Finally, the boosted memory CD8+ T cells resulted in increased protection
    against Listeria monocytogenes expressing the vaccine antigen, but only for the
    duration that the vaccine antigen was archived. These findings outline a novel
    mechanism by which LNSC archived antigens, in addition to bystander activation,
    can augment memory CD8+ T cell responses during repeated inflammatory insults.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571600/pdf/nihpp-rs3307809v1.pdf
  image: /images/2023-tamburini-37841845.jpg
- pubmed: https://pubmed.ncbi.nlm.nih.gov/38307020/
  project:
  - project-1
  - core-b
  key: 2024-kim-38307020
  title: Anaerobic respiration of host-derived methionine sulfoxide protects intracellular
    Salmonella from the phagocyte NADPH oxidase
  pmid: PMID 38307020
  date: January 24, 2024
  year: '2024'
  authors:
  - Ju-Sim Kim
  - Lin Liu
  - Sashi Kant
  - David Orlicky
  - Siva Uppalapati
  - Alyssa Margolis
  - Bennett Davenport
  - Thomas Morrison
  - Jennifer Matsuda
  - Michael McClelland
  - Jessica Jones-Carson
  - Andres Vazquez-Torres
  abstract: Intracellular Salmonella experiencing oxidative stress downregulates aerobic
    respiration. To maintain cellular energetics during periods of oxidative stress,
    intracellular Salmonella must utilize terminal electron acceptors of lower energetic
    value than molecular oxygen. We show here that intracellular Salmonella undergoes
    anaerobic respiration during adaptation to the respiratory burst of the phagocyte
    NADPH oxidase in macrophages and in mice. Reactive oxygen species generated by
    phagocytes oxidize methionine, generating methionine sulfoxide. Anaerobic Salmonella
    uses the molybdenum cofactor-containing DmsABC enzymatic complex to reduce methionine
    sulfoxide. The enzymatic activity of the methionine sulfoxide reductase DmsABC
    helps Salmonella maintain an alkaline cytoplasm that supports the synthesis of
    the antioxidant hydrogen sulfide via cysteine desulfuration while providing a
    source of methionine and fostering redox balancing by associated dehydrogenases.
    Our investigations demonstrate that nontyphoidal Salmonella responding to oxidative
    stress exploits the anaerobic metabolism associated with dmsABC gene products,
    a pathway that has accrued inactivating mutations in human-adapted typhoidal serovars.
- pubmed: https://pubmed.ncbi.nlm.nih.gov/24905362/
  project: project-2
  key: 2014-tamburini-24905362
  title: Antigen capture and archiving by lymphatic endothelial cells following vaccination
    or viral infection
  pmid: PMID 24905362
  date: June 06, 2014
  year: '2014'
  authors:
  - Beth Tamburini
  - Matthew Burchill
  - Ross Kedl
  abstract: Antigen derived from viral infections with influenza and vesicular stomatitis
    virus can persist after resolution of infection. Here we show that antigen can
    similarly persist for weeks following viral challenge and vaccination. Antigen
    is captured by lymphatic endothelial cells (LECs) under conditions that induce
    LEC proliferation. Consistent with published data showing that viral antigen persistence
    impacts the function of circulating memory T cells, we find that vaccine-elicited
    antigen persistence, found on LECs, positively influences the degree of protective
    immunity provided by circulating memory CD8(+) T cells. The coupling of LEC proliferation
    and antigen capture identifies a mechanism by which the LECs store, or 'archive',
    antigens for extended periods of time after antigen challenge, thereby increasing
    IFNγ/IL-2 production and enhancing protection against infection. These findings
    therefore have the potential to have an impact on future vaccination strategies
    and our understanding of the role for persisting antigen in both vaccine and infectious
    settings.
  pdf: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073648/pdf/nihms591068.pdf
  image: /images/2014-tamburini-24905362.jpg