IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques

A. M. Ortiz, Z. A. Klase, S. R. DiNapoli, I. Vujkovic-Cvijin, K. Carmack, M. R. Perkins, N. Calantone, C. L. Vinton, N. E. Riddick, J. Gallagher, N. R. Klatt, J. M. McCune, Jacob Estes, M. Paiardini, J. M. Brenchley

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Increased mortality in antiretroviral (ARV)-treated, HIV-infected individuals has been attributed to persistent immune dysfunction, in part due to abnormalities at the gastrointestinal barrier. In particular, the poor reconstitution of gastrointestinal Th17 cells correlates with residual translocation of dysbiotic, immunostimulatory microflora across a compromised intestinal epithelial barrier. We have previously demonstrated that oral probiotics promote increased intestinal CD4 + T-cell reconstitution during ARV treatment in a non-human primate model of HIV infection; however, essential mucosal T-cell subsets, such as Th17 cells, had limited recovery. Here, we sought to promote Th17 cell recovery by administering interleukin (IL)-21 to a limited number of ARV-treated, probiotic-supplemented, Simian Immunodeficiency Virus (SIV)-infected pigtailed macaques. We demonstrate that probiotic and IL-21 supplementation of ARVs are associated with enhanced polyfunctional Th17 expansion and reduced markers of microbial translocation and dysbiosis as compared with infected controls receiving ARVs alone. Importantly, treatment resulted in fewer morbidities compared with controls, and was independent of increased immune activation or loss of viral suppression. We propose that combining ARVs with therapeutics aimed at restoring intestinal stasis may significantly improve disease prognosis of ARV-treated, HIV-infected individuals.

Original languageEnglish (US)
Pages (from-to)458-467
Number of pages10
JournalMucosal Immunology
Volume9
Issue number2
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

Fingerprint

Th17 Cells
Simian Immunodeficiency Virus
Microbiota
Probiotics
Macaca
Dysbiosis
HIV
T-Lymphocyte Subsets
Primates
HIV Infections
Therapeutics
Morbidity
T-Lymphocytes
Mortality
interleukin-21

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Ortiz, A. M., Klase, Z. A., DiNapoli, S. R., Vujkovic-Cvijin, I., Carmack, K., Perkins, M. R., ... Brenchley, J. M. (2016). IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques. Mucosal Immunology, 9(2), 458-467. https://doi.org/10.1038/mi.2015.75

IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques. / Ortiz, A. M.; Klase, Z. A.; DiNapoli, S. R.; Vujkovic-Cvijin, I.; Carmack, K.; Perkins, M. R.; Calantone, N.; Vinton, C. L.; Riddick, N. E.; Gallagher, J.; Klatt, N. R.; McCune, J. M.; Estes, Jacob; Paiardini, M.; Brenchley, J. M.

In: Mucosal Immunology, Vol. 9, No. 2, 01.03.2016, p. 458-467.

Research output: Contribution to journalArticle

Ortiz, AM, Klase, ZA, DiNapoli, SR, Vujkovic-Cvijin, I, Carmack, K, Perkins, MR, Calantone, N, Vinton, CL, Riddick, NE, Gallagher, J, Klatt, NR, McCune, JM, Estes, J, Paiardini, M & Brenchley, JM 2016, 'IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques', Mucosal Immunology, vol. 9, no. 2, pp. 458-467. https://doi.org/10.1038/mi.2015.75
Ortiz, A. M. ; Klase, Z. A. ; DiNapoli, S. R. ; Vujkovic-Cvijin, I. ; Carmack, K. ; Perkins, M. R. ; Calantone, N. ; Vinton, C. L. ; Riddick, N. E. ; Gallagher, J. ; Klatt, N. R. ; McCune, J. M. ; Estes, Jacob ; Paiardini, M. ; Brenchley, J. M. / IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques. In: Mucosal Immunology. 2016 ; Vol. 9, No. 2. pp. 458-467.
@article{ebb4b36bb0a64ca393cdf0570d83acff,
title = "IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques",
abstract = "Increased mortality in antiretroviral (ARV)-treated, HIV-infected individuals has been attributed to persistent immune dysfunction, in part due to abnormalities at the gastrointestinal barrier. In particular, the poor reconstitution of gastrointestinal Th17 cells correlates with residual translocation of dysbiotic, immunostimulatory microflora across a compromised intestinal epithelial barrier. We have previously demonstrated that oral probiotics promote increased intestinal CD4 + T-cell reconstitution during ARV treatment in a non-human primate model of HIV infection; however, essential mucosal T-cell subsets, such as Th17 cells, had limited recovery. Here, we sought to promote Th17 cell recovery by administering interleukin (IL)-21 to a limited number of ARV-treated, probiotic-supplemented, Simian Immunodeficiency Virus (SIV)-infected pigtailed macaques. We demonstrate that probiotic and IL-21 supplementation of ARVs are associated with enhanced polyfunctional Th17 expansion and reduced markers of microbial translocation and dysbiosis as compared with infected controls receiving ARVs alone. Importantly, treatment resulted in fewer morbidities compared with controls, and was independent of increased immune activation or loss of viral suppression. We propose that combining ARVs with therapeutics aimed at restoring intestinal stasis may significantly improve disease prognosis of ARV-treated, HIV-infected individuals.",
author = "Ortiz, {A. M.} and Klase, {Z. A.} and DiNapoli, {S. R.} and I. Vujkovic-Cvijin and K. Carmack and Perkins, {M. R.} and N. Calantone and Vinton, {C. L.} and Riddick, {N. E.} and J. Gallagher and Klatt, {N. R.} and McCune, {J. M.} and Jacob Estes and M. Paiardini and Brenchley, {J. M.}",
year = "2016",
month = "3",
day = "1",
doi = "10.1038/mi.2015.75",
language = "English (US)",
volume = "9",
pages = "458--467",
journal = "Mucosal Immunology",
issn = "1933-0219",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - IL-21 and probiotic therapy improve Th17 frequencies, microbial translocation, and microbiome in ARV-treated, SIV-infected macaques

AU - Ortiz, A. M.

AU - Klase, Z. A.

AU - DiNapoli, S. R.

AU - Vujkovic-Cvijin, I.

AU - Carmack, K.

AU - Perkins, M. R.

AU - Calantone, N.

AU - Vinton, C. L.

AU - Riddick, N. E.

AU - Gallagher, J.

AU - Klatt, N. R.

AU - McCune, J. M.

AU - Estes, Jacob

AU - Paiardini, M.

AU - Brenchley, J. M.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Increased mortality in antiretroviral (ARV)-treated, HIV-infected individuals has been attributed to persistent immune dysfunction, in part due to abnormalities at the gastrointestinal barrier. In particular, the poor reconstitution of gastrointestinal Th17 cells correlates with residual translocation of dysbiotic, immunostimulatory microflora across a compromised intestinal epithelial barrier. We have previously demonstrated that oral probiotics promote increased intestinal CD4 + T-cell reconstitution during ARV treatment in a non-human primate model of HIV infection; however, essential mucosal T-cell subsets, such as Th17 cells, had limited recovery. Here, we sought to promote Th17 cell recovery by administering interleukin (IL)-21 to a limited number of ARV-treated, probiotic-supplemented, Simian Immunodeficiency Virus (SIV)-infected pigtailed macaques. We demonstrate that probiotic and IL-21 supplementation of ARVs are associated with enhanced polyfunctional Th17 expansion and reduced markers of microbial translocation and dysbiosis as compared with infected controls receiving ARVs alone. Importantly, treatment resulted in fewer morbidities compared with controls, and was independent of increased immune activation or loss of viral suppression. We propose that combining ARVs with therapeutics aimed at restoring intestinal stasis may significantly improve disease prognosis of ARV-treated, HIV-infected individuals.

AB - Increased mortality in antiretroviral (ARV)-treated, HIV-infected individuals has been attributed to persistent immune dysfunction, in part due to abnormalities at the gastrointestinal barrier. In particular, the poor reconstitution of gastrointestinal Th17 cells correlates with residual translocation of dysbiotic, immunostimulatory microflora across a compromised intestinal epithelial barrier. We have previously demonstrated that oral probiotics promote increased intestinal CD4 + T-cell reconstitution during ARV treatment in a non-human primate model of HIV infection; however, essential mucosal T-cell subsets, such as Th17 cells, had limited recovery. Here, we sought to promote Th17 cell recovery by administering interleukin (IL)-21 to a limited number of ARV-treated, probiotic-supplemented, Simian Immunodeficiency Virus (SIV)-infected pigtailed macaques. We demonstrate that probiotic and IL-21 supplementation of ARVs are associated with enhanced polyfunctional Th17 expansion and reduced markers of microbial translocation and dysbiosis as compared with infected controls receiving ARVs alone. Importantly, treatment resulted in fewer morbidities compared with controls, and was independent of increased immune activation or loss of viral suppression. We propose that combining ARVs with therapeutics aimed at restoring intestinal stasis may significantly improve disease prognosis of ARV-treated, HIV-infected individuals.

UR - http://www.scopus.com/inward/record.url?scp=84961806957&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961806957&partnerID=8YFLogxK

U2 - 10.1038/mi.2015.75

DO - 10.1038/mi.2015.75

M3 - Article

C2 - 26286233

AN - SCOPUS:84961806957

VL - 9

SP - 458

EP - 467

JO - Mucosal Immunology

JF - Mucosal Immunology

SN - 1933-0219

IS - 2

ER -