All Publications


  • The immunoregulatory landscape of human tuberculosis granulomas. Nature immunology McCaffrey, E. F., Donato, M., Keren, L., Chen, Z., Delmastro, A., Fitzpatrick, M. B., Gupta, S., Greenwald, N. F., Baranski, A., Graf, W., Kumar, R., Bosse, M., Fullaway, C. C., Ramdial, P. K., Forgó, E., Jojic, V., Van Valen, D., Mehra, S., Khader, S. A., Bendall, S. C., van de Rijn, M., Kalman, D., Kaushal, D., Hunter, R. L., Banaei, N., Steyn, A. J., Khatri, P., Angelo, M. 2022

    Abstract

    Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB. We constructed a comprehensive atlas that maps 19 cell subsets across 8 spatial microenvironments. This atlas shows an IFN-γ-depleted microenvironment enriched for TGF-β, regulatory T cells and IDO1+ PD-L1+ myeloid cells. In a further transcriptomic meta-analysis of peripheral blood from patients with TB, immunoregulatory trends mirror those identified by granuloma imaging. Notably, PD-L1 expression is associated with progression to active TB and treatment response. These data indicate that in TB granulomas, there are local spatially coordinated immunoregulatory programs with systemic manifestations that define active TB.

    View details for DOI 10.1038/s41590-021-01121-x

    View details for PubMedID 35058616

  • Rhesus Macaque CODEX Multiplexed Immunohistochemistry Panel for Studying Immune Responses During Ebola Infection FRONTIERS IN IMMUNOLOGY Jiang, S., Mukherjee, N., Bennett, R. S., Chen, H., Logue, J., Dighero-Kemp, B., Kurtz, J. R., Adams, R., Phillips, D., Schuerch, C. M., Goltsev, Y., Hickey, J. W., McCaffrey, E. F., Delmastro, A., Chu, P., Reader, J., Keesler, R., Galvan, J. A., Zlobec, I., Van Rompay, K. A., Liu, D. X., Hensley, L. E., Nolan, G. P., McIlwain, D. R. 2021; 12: 729845

    Abstract

    Non-human primate (NHP) animal models are an integral part of the drug research and development process. For some biothreat pathogens, animal model challenge studies may offer the only possibility to evaluate medical countermeasure efficacy. A thorough understanding of host immune responses in such NHP models is therefore vital. However, applying antibody-based immune characterization techniques to NHP models requires extensive reagent development for species compatibility. In the case of studies involving high consequence pathogens, further optimization for use of inactivated samples may be required. Here, we describe the first optimized CO-Detection by indEXing (CODEX) multiplexed tissue imaging antibody panel for deep profiling of spatially resolved single-cell immune responses in rhesus macaques. This 21-marker panel is composed of a set of 18 antibodies that stratify major immune cell types along with a set three Ebola virus (EBOV)-specific antibodies. We validated these two sets of markers using immunohistochemistry and CODEX in fully inactivated Formalin-Fixed Paraffin-Embedded (FFPE) tissues from mock and EBOV challenged macaques respectively and provide an efficient framework for orthogonal validation of multiple antibody clones using CODEX multiplexed tissue imaging. We also provide the antibody clones and oligonucleotide tag sequences as a valuable resource for other researchers to recreate this reagent set for future studies of tissue immune responses to EBOV infection and other diseases.

    View details for DOI 10.3389/fimmu.2021.729845

    View details for Web of Science ID 000732063400001

    View details for PubMedID 34938283

    View details for PubMedCentralID PMC8685521