Maintenance of Intestinal Th17 Cells and Reduced Microbial Translocation in SIV-infected Rhesus Macaques Treated with Interleukin (IL)-21

Suresh Pallikkuth, Luca Micci, Zachary S. Ende, Robin I. Iriele, Barbara Cervasi, Benton Lawson, Colleen S. McGary, Kenneth A. Rogers, James G. Else, Guido Silvestri, Kirk Easley, Jacob D. Estes, Francois Villinger, Savita Pahwa, Mirko Paiardini

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

In pathogenic HIV and SIV infections of humans and rhesus macaques (RMs), preferential depletion of CD4+ Th17 cells correlates with mucosal immune dysfunction and disease progression. Interleukin (IL)-21 promotes differentiation of Th17 cells, long-term maintenance of functional CD8+ T cells, and differentiation of memory B cells and antibody-secreting plasma cells. We hypothesized that administration of IL-21 will improve mucosal function in the context of pathogenic HIV/SIV infections. To test this hypothesis, we infected 12 RMs with SIVmac239 and at day 14 post-infection treated six of them with rhesus rIL-21-IgFc. IL-21-treatment was safe and did not increase plasma viral load or systemic immune activation. Compared to untreated animals, IL-21-treated RMs showed (i) higher expression of perforin and granzyme B in total and SIV-specific CD8+ T cells and (ii) higher levels of intestinal Th17 cells. Remarkably, increased levels of Th17 cells were associated with reduced levels of intestinal T cell proliferation, microbial translocation and systemic activation/inflammation in the chronic infection. In conclusion, IL-21-treatment in SIV-infected RMs improved mucosal immune function through enhanced preservation of Th17 cells. Further preclinical studies of IL-21 may be warranted to test its potential use during chronic infection in conjunction with antiretroviral therapy.

Original languageEnglish (US)
Article numbere1003471
JournalPLoS pathogens
Volume9
Issue number7
DOIs
StatePublished - Jul 2013

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Pallikkuth, S., Micci, L., Ende, Z. S., Iriele, R. I., Cervasi, B., Lawson, B., McGary, C. S., Rogers, K. A., Else, J. G., Silvestri, G., Easley, K., Estes, J. D., Villinger, F., Pahwa, S., & Paiardini, M. (2013). Maintenance of Intestinal Th17 Cells and Reduced Microbial Translocation in SIV-infected Rhesus Macaques Treated with Interleukin (IL)-21. PLoS pathogens, 9(7), [e1003471]. https://doi.org/10.1371/journal.ppat.1003471