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The immunoregulatory landscape of human tuberculosis granulomas.
McCaffrey, Erin F; Donato, Michele; Keren, Leeat; Chen, Zhenghao; Delmastro, Alea; Fitzpatrick, Megan B; Gupta, Sanjana; Greenwald, Noah F; Baranski, Alex; Graf, William; Kumar, Rashmi; Bosse, Marc; Fullaway, Christine Camacho; Ramdial, Pratista K; Forgó, Erna; Jojic, Vladimir; Van Valen, David; Mehra, Smriti; Khader, Shabaana A; Bendall, Sean C; van de Rijn, Matt; Kalman, Daniel; Kaushal, Deepak; Hunter, Robert L; Banaei, Niaz; Steyn, Adrie J C; Khatri, Purvesh; Angelo, Michael.
Afiliação
  • McCaffrey EF; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Donato M; Department of Medicine, Division of Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA, USA.
  • Keren L; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Chen Z; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Delmastro A; Calico Life Sciences LLC, South San Francisco, CA, USA.
  • Fitzpatrick MB; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Gupta S; Department of Pathology, University of Wisconsin, Madison, WI, USA.
  • Greenwald NF; Department of Medicine, Division of Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA, USA.
  • Baranski A; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Graf W; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Kumar R; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Bosse M; Division of Biology and Bioengineering, California Institute of Technology, Pasadena, CA, USA.
  • Fullaway CC; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Ramdial PK; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Forgó E; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Jojic V; Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa.
  • Van Valen D; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Mehra S; Calico Life Sciences LLC, South San Francisco, CA, USA.
  • Khader SA; Division of Biology and Bioengineering, California Institute of Technology, Pasadena, CA, USA.
  • Bendall SC; Texas Biomedical Research Institute, San Antonio, TX, USA.
  • van de Rijn M; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
  • Kalman D; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Kaushal D; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Hunter RL; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
  • Banaei N; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
  • Steyn AJC; Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center at Houston, Houston, TX, USA.
  • Khatri P; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Angelo M; Division of Infectious Diseases & Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
Nat Immunol ; 23(2): 318-329, 2022 02.
Article em En | MEDLINE | ID: mdl-35058616
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-ß, 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Granuloma Tipo de estudo: Systematic_reviews Limite: Humans Idioma: En Revista: Nat Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tuberculose / Granuloma Tipo de estudo: Systematic_reviews Limite: Humans Idioma: En Revista: Nat Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos