title: Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection.
abstract: Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TF(Δ) ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2-like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth.
authors.affiliation: Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Sambasivan
authors.initials: S
authors.lastname: Venkatasubramanian
authors.affiliation: Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Tripathi
authors.affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Torry
authors.initials: T
authors.lastname: Tucker
authors.affiliation: Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Padmaja
authors.initials: P
authors.lastname: Paidipally
authors.affiliation: Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Cheekatla
authors.affiliation: Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Elwyn
authors.initials: E
authors.lastname: Welch
authors.affiliation: Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Anjana
authors.initials: A
authors.lastname: Raghunath
authors.affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Jeffers
authors.affiliation: Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Tvinnereim
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Schechter
authors.affiliation: Investigative Medicine Branch, Laboratory of Immune Regulation, Centro de Pesquisas Gonçalo Moniz (CPqGM), Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil.|Research Center, Brazilian Institute for Tuberculosis Research, Salvador, Bahia, Brazil.
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Andrade
authors.affiliation: Department of Medicine, The University of North Carolina at Chapel Hill School of Medicine, NC, USA.
authors.forename: Nizel
authors.initials: N
authors.lastname: Mackman
authors.affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Idell
authors.affiliation: Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Vankayalapati
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000209:etiology / Q000276:immunology*; D001777:Blood Coagulation; D002454:Cell Differentiation; D005260:Female; D005337:Fibrin / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D011014:Pneumonia / Q000209:etiology / Q000276:immunology*; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D014375:Tuberculoma / Q000209:etiology / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000276:immunology*
chemical_list: D005337:Fibrin; D013925:Thromboplastin
keywords: Apoptosis; IL-10; M. tuberculosis; Macrophage; Tissue factor