Tissue distribution and antiviral response of primary human dendritic cells
Final Report Abstract
During my postdoc in the lab of Boris Reizis at NYU Langone, I was working on the distribution of myeloid cells, with a focus on dendritic cells, in the healthy state in mice and humans. A significant part of the project was designated to designing multiplex imaging panels to show all relevant cell types in the human body, focusing on plasmacytoid and conventional dendritic cells (DC) as part of the Human Immunology Project Consortium (HIPC). We were able to look at changes in the DC niche over different age groups using lymph nodes and spleens from healthy organ donors. The DCs were mostly located in the interfollicular T cell areas, but changes in the adjacent cells were seen with aging and concurrent conditions (e.g. BMI). We also compared these distributions to the ones seen in different inflammatory benign disease, e.g. Castleman disease, and were able to show additional DC niches in these conditions. To ensure thorough analysis of the spatial data sets, we established a computational pipeline for the analysis of multiplexed tissue images, which we also implemented as a web-based resource (phenoptics). Researchers only need to feed an image with a corresponding segmentation file into the system and are able to walk through different modules for dimensionality reduction (UMAP), clustering, cell type identification and – after visual confirmation of the results – interaction analysis using pairwise log-odds analysis, incidence probability plots and pairwise correlation functions (PCF). Phenoptics was used to look at the distribution of major cell types in murine skin-draining lymph nodes and to analyze rapid interactions over the time of a viral footpad infection. During the early phase of infection (15 hours) we saw a massive influx of neutrophils, but also transient interactions of VSV-infected subcapsular macrophages with plasmacytoid dendritic cells (pDCs). As a side-project within my HIPC collaboration, I additionally imaged immune cells within the pancreatic tissue looking at a range of organ donor samples. Changes in macrophage subtypes, T cell density, and islet proliferation were seen for lean patients, obese patients and patients with diabetes type II.
Publications
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Putting the Pieces on the Board: Mapping SLE Nephritis Biopsies from the Accelerating Medicines Project Using High-Density Immunofluorescence Imaging.. Meeting: ACR Convergence 2021
Craig Smuda, Anna Eichinger, Robert Clancy, Jill Buyon & Boris Reizis
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Comprehensive characterization of human dendritic cell composition and function, specifically as it relates to immune responses to infection and vaccination – Aim 2: Spatial distribution and functional states of DCs in human tissues. Talk HIPC Meeting November 2022 at Columbia University (Human Immunology Project Subgroup Meeting; NIH U19-AI128949-05)
Anna Eichinger
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Cutting Edge: TLR2 Signaling in B Cells Promotes Autoreactivity to DNA via IL-6 Secretion. The Journal of Immunology, 211(10), 1475-1480.
Soni, Chetna; Makita, Sohei; Eichinger, Anna; Serpas, Lee; Sisirak, Vanja & Reizis, Boris
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Hematoxylin and Eosin staining of PhenoCycler® Fusion flow cell slides. Journal of Histotechnology, 46(4), 203-206.
Shiomi, Tomoe; Eichinger, Anna & Chiriboga, Luis
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Single cell multi-omics reveals unique populations, cell interactions and signaling pathways that underlie Kikuchi-Fujimoto disease. Meeting: USCAP New Orleans, 2023
Vinodh Pillai, David Smith, Anna Eichinger, … & Boris Reizis
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A pipeline for spatial analysis of dendritic cell neighborhoods in human lymph node.. Poster at General Human Immunology Project Meeting 2024
Eichinger Anna, Weisberg Stuart, … Farber Donna & Boris Reizis
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Obesity promotes an immunogenic landscape of macrophage T cell interaction in human pancreas. Meeting: Immunology2024TM Chicago. Abstract number 1206-5491
Kranthi Tanagala, Alexey Koshkin, Aoife Young, Anna Eichinger, …, Boris Reizis, Donna Farber & Stuart Weisberg
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Spatial immune profiling in human pancreas reveals pathological correlates of disease risk. Meeting ACLPS Laboratory Medicine 2024
Stuart Weisberg, Anna Eichinger, …, Boris Reizis & Donna Farber
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Spatial and single cell mapping of castleman disease reveals key stromal cell types and cytokine pathways. Nature Communications, 16(1).
Smith, David; Eichinger, Anna; Fennell, Éanna; Xu-Monette, Zijun Y.; Rech, Andrew; Wang, Julia; Esteva, Eduardo; Seyedian, Arta; Yang, Xiaoxu; Zhang, Mei; Martinez, Dan; Tan, Kai; Luo, Minjie; Young, Katherine J.; Murray, Paul G.; Park, Christopher; Reizis, Boris & Pillai, Vinodh
