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.

journal_name

Eur J Immunol

authors

Venkatasubramanian S,Tripathi D,Tucker T,Paidipally P,Cheekatla S,Welch E,Raghunath A,Jeffers A,Tvinnereim AR,Schechter ME,Andrade BB,Mackman N,Idell S,Vankayalapati R

doi

10.1002/eji.201545817

subject

Has Abstract

pub_date

2016-02-01 00:00:00

pages

464-79

issue

2

eissn

0014-2980

issn

1521-4141

journal_volume

46

pub_type

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