Suppressed Th17 levels correlate with elevated PIAS3, SHP2, and SOCS3 expression in CD4 T cells during acute simian immunodeficiency virus infection

Sandra L. Bixler, Netanya G. Sandler, Daniel C. Douek, Joseph J. Mattapallil

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

T helper 17 (Th17) cells play an important role in mucosal immune homeostasis and maintaining the integrity of the mucosal epithelial barrier. Loss of Th17 cells has been extensively documented during human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections. The lack of effective repopulation of Th17 cells has been associated with chronic immune activation mediated by the translocation of microbial products. Using ex vivo analysis of purified peripheral blood CD4 T cells from SIV-infected rhesus macaques, we show that the suppression of interleukin-17 (IL-17) expression correlated with upregulated expression of negative regulatory genes PIAS3, SHP2, and SOCS3 in CD4 T cells. Suppressed Th17 expression was accompanied by elevated levels of soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) in the plasma during early stages of infection. Plasma viral loads rather than sCD14 or LBP levels correlated with acute immune activation. Additionally, we observed a significant increase in the expression of CD14 on peripheral blood monocytes that correlated with IL-23 expression and markers of microbial translocation. Taken together, our results provide new insights into the early events associated with acute SIV pathogenesis and suggest additional mechanisms playing a role in suppression of Th17 cells.

Original languageEnglish (US)
Pages (from-to)7093-7101
Number of pages9
JournalJournal of Virology
Volume87
Issue number12
DOIs
StatePublished - Jun 2013
Externally publishedYes

Fingerprint

Simian immunodeficiency virus
Th17 Cells
Simian Immunodeficiency Virus
Virus Diseases
T-lymphocytes
T-Lymphocytes
infection
lipopolysaccharides
binding proteins
cells
Interleukin-23
Interleukin-17
blood
Human immunodeficiency virus
Regulator Genes
viral load
Macaca mulatta
regulator genes
Viral Load
monocytes

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Suppressed Th17 levels correlate with elevated PIAS3, SHP2, and SOCS3 expression in CD4 T cells during acute simian immunodeficiency virus infection. / Bixler, Sandra L.; Sandler, Netanya G.; Douek, Daniel C.; Mattapallil, Joseph J.

In: Journal of Virology, Vol. 87, No. 12, 06.2013, p. 7093-7101.

Research output: Contribution to journalArticle

Bixler, Sandra L. ; Sandler, Netanya G. ; Douek, Daniel C. ; Mattapallil, Joseph J. / Suppressed Th17 levels correlate with elevated PIAS3, SHP2, and SOCS3 expression in CD4 T cells during acute simian immunodeficiency virus infection. In: Journal of Virology. 2013 ; Vol. 87, No. 12. pp. 7093-7101.
@article{eb62bd99d5af4031b3a25d5becc56eb0,
title = "Suppressed Th17 levels correlate with elevated PIAS3, SHP2, and SOCS3 expression in CD4 T cells during acute simian immunodeficiency virus infection",
abstract = "T helper 17 (Th17) cells play an important role in mucosal immune homeostasis and maintaining the integrity of the mucosal epithelial barrier. Loss of Th17 cells has been extensively documented during human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections. The lack of effective repopulation of Th17 cells has been associated with chronic immune activation mediated by the translocation of microbial products. Using ex vivo analysis of purified peripheral blood CD4 T cells from SIV-infected rhesus macaques, we show that the suppression of interleukin-17 (IL-17) expression correlated with upregulated expression of negative regulatory genes PIAS3, SHP2, and SOCS3 in CD4 T cells. Suppressed Th17 expression was accompanied by elevated levels of soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) in the plasma during early stages of infection. Plasma viral loads rather than sCD14 or LBP levels correlated with acute immune activation. Additionally, we observed a significant increase in the expression of CD14 on peripheral blood monocytes that correlated with IL-23 expression and markers of microbial translocation. Taken together, our results provide new insights into the early events associated with acute SIV pathogenesis and suggest additional mechanisms playing a role in suppression of Th17 cells.",
author = "Bixler, {Sandra L.} and Sandler, {Netanya G.} and Douek, {Daniel C.} and Mattapallil, {Joseph J.}",
year = "2013",
month = "6",
doi = "10.1128/JVI.00600-13",
language = "English (US)",
volume = "87",
pages = "7093--7101",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Suppressed Th17 levels correlate with elevated PIAS3, SHP2, and SOCS3 expression in CD4 T cells during acute simian immunodeficiency virus infection

AU - Bixler, Sandra L.

AU - Sandler, Netanya G.

AU - Douek, Daniel C.

AU - Mattapallil, Joseph J.

PY - 2013/6

Y1 - 2013/6

N2 - T helper 17 (Th17) cells play an important role in mucosal immune homeostasis and maintaining the integrity of the mucosal epithelial barrier. Loss of Th17 cells has been extensively documented during human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections. The lack of effective repopulation of Th17 cells has been associated with chronic immune activation mediated by the translocation of microbial products. Using ex vivo analysis of purified peripheral blood CD4 T cells from SIV-infected rhesus macaques, we show that the suppression of interleukin-17 (IL-17) expression correlated with upregulated expression of negative regulatory genes PIAS3, SHP2, and SOCS3 in CD4 T cells. Suppressed Th17 expression was accompanied by elevated levels of soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) in the plasma during early stages of infection. Plasma viral loads rather than sCD14 or LBP levels correlated with acute immune activation. Additionally, we observed a significant increase in the expression of CD14 on peripheral blood monocytes that correlated with IL-23 expression and markers of microbial translocation. Taken together, our results provide new insights into the early events associated with acute SIV pathogenesis and suggest additional mechanisms playing a role in suppression of Th17 cells.

AB - T helper 17 (Th17) cells play an important role in mucosal immune homeostasis and maintaining the integrity of the mucosal epithelial barrier. Loss of Th17 cells has been extensively documented during human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections. The lack of effective repopulation of Th17 cells has been associated with chronic immune activation mediated by the translocation of microbial products. Using ex vivo analysis of purified peripheral blood CD4 T cells from SIV-infected rhesus macaques, we show that the suppression of interleukin-17 (IL-17) expression correlated with upregulated expression of negative regulatory genes PIAS3, SHP2, and SOCS3 in CD4 T cells. Suppressed Th17 expression was accompanied by elevated levels of soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) in the plasma during early stages of infection. Plasma viral loads rather than sCD14 or LBP levels correlated with acute immune activation. Additionally, we observed a significant increase in the expression of CD14 on peripheral blood monocytes that correlated with IL-23 expression and markers of microbial translocation. Taken together, our results provide new insights into the early events associated with acute SIV pathogenesis and suggest additional mechanisms playing a role in suppression of Th17 cells.

UR - http://www.scopus.com/inward/record.url?scp=84878574716&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878574716&partnerID=8YFLogxK

U2 - 10.1128/JVI.00600-13

DO - 10.1128/JVI.00600-13

M3 - Article

VL - 87

SP - 7093

EP - 7101

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 12

ER -