Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy

Melissa E. Schechter, Bruno B. Andrade, Tianyu He, George Haret Richter, Kevin W. Tosh, Benjamin B. Policicchio, Amrit Singh, Kevin D. Raehtz, Virginia Sheikh, Dongying Ma, Egidio Brocca-Cofano, Cristian Apetrei, Russel Tracy, Ruy M. Ribeiro, Alan Sher, Ivo M.B. Francischetti, Ivona Pandrea, Irini Sereti

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. A better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X. This subset of monocytes expressing TF had a distinct gene signature with up-regulated innate immune markers and evidence of robust production of multiple proinflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6, ex vivo and in vitro upon lipopolysaccharide stimulation.We validated our findings in a nonhuman primatemodel, showing that TF-expressing inflammatory monocytes were associated with simian immunodeficiency virus (SIV)-related coagulopathy in the progressive [pigtail macaques (PTMs)] but not in the nonpathogenic (African green monkeys) SIV infection model. Last, Ixolaris, an anticoagulant that inhibits the TF pathway, was tested and potently blocked functional TF activity in vitro in HIV and SIV infection without affecting monocyte responses to Toll-like receptor stimulation. Strikingly, in vivo treatment of SIV-infected PTMs with Ixolaris was associated with significant decreases in D-dimer and immune activation. These data suggest that TF-expressing monocytes are at the epicenter of inflammation and coagulation in chronic HIV and SIV infection and may represent a potential therapeutic target.

Original languageEnglish (US)
Article numberaam5441
JournalScience translational medicine
Issue number405
StatePublished - Aug 30 2017
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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