Biomarkers of cellular stress do not associate with scd14 in progressive hiv and siv infections in vivo

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Microbial translocation occurs after damage to the structural and/or immunolog-ical barrier of the gastrointestinal (GI) tract into circulation. Microbial components that trans-locate 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 simul-taneously 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 dy-ing 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 an-tiretroviral 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.

Original languageEnglish (US)
Pages (from-to)68-88
Number of pages21
JournalPathogens and Immunity
Volume5
Issue number1
DOIs
StatePublished - 2020

Keywords

  • HIV
  • Inflammation
  • Microbial translocation
  • SIV

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Microbiology (medical)
  • Immunology
  • Molecular Biology

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