Reduced inflammation and lymphoid tissue immunopathology in rhesus macaques receiving anti-tumor necrosis factor treatment during primary simian immunodeficiency virus infection

Brian Tabb, David R. Morcock, Charles M. Trubey, Octavio A. Quiñones, Xing Pei Hao, Jeremy Smedley, Rhonda MacAllister, Michael Piatak, Levelle D. Harris, Mirko Paiardini, Guido Silvestri, Jason M. Brenchley, W. Gregory Alvord, Jeffrey D. Lifson, Jacob D. Estes

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Background. Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections induce robust, generalized inflammatory responses that begin during acute infection and lead to pathological systemic immune activation, fibrotic damage of lymphoid tissues, and CD4+ T-cell loss, pathogenic processes that contribute to disease progression.Methods. To better understand the contribution of tumor necrosis factor (TNF), a key regulator of acute inflammation, to lentiviral pathogenesis, rhesus macaques newly infected with SIVmac239 were treated for 12 weeks in a pilot study with adalimumab (Humira), a human anti-TNF monoclonal antibody.Results. Adalimumab did not affect plasma SIV RNA levels or measures of T-cell immune activation (CD38 or Ki67) in peripheral blood or lymph node T cells. However, compared with untreated rhesus macaques, adalimumab-treated rhesus macaques showed attenuated expression of proinflammatory genes, decreased infiltration of polymorphonuclear cells into the T-cell zone of lymphoid tissues, and weaker antiinflammatory regulatory responses to SIV infection (ie, fewer presumed alternatively activated [ie, CD163+] macrophages, interleukin 10-producing cells, and transforming growth factor -producing cells), along with reduced lymphoid tissue fibrosis and better preservation of CD4+ T cells.Conclusions. While HIV/SIV replication drives pathogenesis, these data emphasize the contribution of the inflammatory response to lentiviral infection to overall pathogenesis, and they suggest that early modulation of the inflammatory response may help attenuate disease progression.

Original languageEnglish (US)
Pages (from-to)880-892
Number of pages13
JournalJournal of Infectious Diseases
Volume207
Issue number6
DOIs
StatePublished - Feb 28 2013

Keywords

  • SIV
  • Sooty mangabey
  • TGFb
  • TNF
  • adalimumab
  • collagen
  • fibrosis
  • inflammation
  • lymph node
  • macrophage
  • rhesus macaque

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Tabb, B., Morcock, D. R., Trubey, C. M., Quiñones, O. A., Hao, X. P., Smedley, J., MacAllister, R., Piatak, M., Harris, L. D., Paiardini, M., Silvestri, G., Brenchley, J. M., Alvord, W. G., Lifson, J. D., & Estes, J. D. (2013). Reduced inflammation and lymphoid tissue immunopathology in rhesus macaques receiving anti-tumor necrosis factor treatment during primary simian immunodeficiency virus infection. Journal of Infectious Diseases, 207(6), 880-892. https://doi.org/10.1093/infdis/jis643