title: Platelets direct monocyte differentiation into epithelioid-like multinucleated giant foam cells with suppressive capacity upon mycobacterial stimulation.
abstract: BACKGROUND
  Epithelioid, foam, and multinucleated giant cells (MNGCs) are characteristics of tuberculosis granulomas, yet the precise genesis and functions of these transformed macrophages are unclear. We evaluated the role of platelets as drivers of macrophage transformation in mycobacterial infection.
  
  
  METHODS
  We employed flow cytometry and microscopy to assess cellular phenotype and phagocytosis. Immune assays allowed quantification of cytokines and chemokines, whereas gene microarray technology was applied to estimate global transcriptome alterations. Immunohistochemical investigations of tuberculosis granulomas substantiated our findings at the site of infection.
  
  
  RESULTS
  Monocytes differentiated in presence of platelets (MP-Macs) acquired a foamy, epithelioid appearance and gave rise to MNGCs (MP-MNGCs). MP-Macs up-regulated activation markers, phagocytosed mycobacteria, and released abundant interleukin 10. Upon extended culture, MP-Macs shared transcriptional features with epithelioid cells and M2 macrophages and up-regulated CXCL5 transcripts. In line with this, CXCL5 concentrations were significantly increased in airways of active tuberculosis patients. The platelet-specific CD42b antigen was detected in MP-Macs, likewise in macrophages, MNGCs, and epithelioid cells within tuberculosis granulomas, along with the platelet aggregation-inducing factor PDPN.
  
  
  CONCLUSIONS
  Platelets drive macrophage differentiation into MNGCs with characteristics of epithelioid, foam, and giant cells observed in tuberculosis granulomas. Our data define platelets as novel participants in tuberculosis pathogenesis.
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Anca
authors.initials: A
authors.lastname: Dorhoi
authors.affiliation: Max Planck Institute for Infection Biology, Core Facility Microarray/Genomics, Berlin, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Mollenkopf
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Pathology, Shanghai Pulmonary Hospital, Tongji University.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Mao
authors.affiliation: Department of Pathology, Shanghai Pulmonary Hospital, Tongji University.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, China.
authors.forename: Aixiao
authors.initials: A
authors.lastname: Bi
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Weber
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Maertzdorf
authors.affiliation: Department of Pathology, Shanghai Pulmonary Hospital, Tongji University.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Bioinformatics Division and Center for Synthetic and Systems Biology, TNLIST, Department of Automation, Tsinghua University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000328:Adult; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism*; D018920:Coculture Techniques; D005260:Female; D005487:Foam Cells / Q000276:immunology* / Q000473:pathology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006099:Granuloma / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D006801:Humans; D056747:Immunomodulation; D016753:Interleukin-10 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D009161:Mycobacterium / Q000276:immunology*; D010587:Phagocytosis; D015539:Platelet Activation; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
chemical_list: D015415:Biomarkers; D008070:Lipopolysaccharides; D016753:Interleukin-10
keywords: CXCL5; macrophage; multinucleated giant cell; platelet; tuberculosis