Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection |
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| Authors: | Sambasivan Venkatasubramanian Deepak Tripathi Torry Tucker Padmaja Paidipally Satyanarayana Cheekatla Elwyn Welch Anjana Raghunath Ann Jeffers Amy R. Tvinnereim Melissa E Schechter Bruno B Andrade Nizel Mackman Steven Idell Ramakrishna Vankayalapati |
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| Affiliation: | 1. Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, Tyler, TX, USA;2. Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, TX, USA;3. Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, MD, USA;4. Investigative Medicine Branch, Laboratory of Immune Regulation, Centro de Pesquisas Gon?alo Moniz (CPqGM), Funda??o Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil;5. Research Center, Brazilian Institute for Tuberculosis Research, Salvador, Bahia, Brazil;6. Department of Medicine, The University of North Carolina at Chapel Hill School of Medicine, NC, USA |
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| 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 (TFΔ) 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. |
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| Keywords: | Apoptosis IL‐10 Macrophage M. tuberculosis Tissue factor |
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