Biomarkers of Cellular Stress Do Not Associate with sCD14 in Progressive HIV and SIV Infections in Vivo

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Carol L. Vinton
Carly E. Starke
Alexandra M. Ortiz
Stephen H. Lai
Jacob K. Flynn
Ornella Sortino
Kenneth Knox
Irini Sereti
Jason Brenchley



Background: Microbial translocation occurs after damage to the structural and/or immunological barrier of the gastrointestinal (GI) tract into circulation. Microbial components that translocate from the lumen of the GI tract directly stimulate the immune system and contribute to inflammation. When microbial translocation becomes chronic, the inflammation has detrimental consequences. Given that microbial translocation is an important phenomenon in many diseases, defining biomarkers that reliably reflect microbial translocation is critical. Measurement of systemic microbial products is difficult since: 1) robust assays to measure microbial antigens simultaneously are lacking; 2) confounding factors influence assays used to detect microbial products; and 3) biological clearance mechanisms limit their detection in circulation. Thus, host proteins produced in response to microbial stimulation are used as surrogates for microbial translocation; however, many of these proteins are also produced in response to host proteins expressed by dying cells.

Methods: We measured plasma levels of biomarkers associated with GI tract damage, immune responses to microbial products, and cell-death in people living with HIV before and after antiretroviral administration, and in macaque nonhuman primates before and after SIV infection.

Results: Proteins secreted during cellular stress (receptor for advanced glycation endproducts - RAGE and high motility group box 1 -HMGB1), which can induce sCD14 production in vitro and in vivo, do not associate with elevated levels of biomarkers associated with microbial translocation in progressively HIV-infected individuals and SIV-infected NHPs.

Conclusions: Bystander cell death and generalized inflammation do not contribute to elevated levels of sCD14 observed in HIV/SIV-infected individuals.


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Author Biography

Jason Brenchley, National Institutes of Health

Dr. Brenchley received a master’s degree from Idaho State University in 1999 and received a Ph.D. from the University of Texas Southwestern Medical Center at Dallas in 2003. He joined NIH as a research fellow, studying immunopathogenesis and mucosal immunology in HIV-infected individuals. Since 2008, he has become an investigator in the Laboratory of Molecular Microbiology and has been a senior investigator since 2013.


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