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Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation.

Publication ,  Journal Article
Palmer, CD; Romero-Tejeda, M; Sirignano, M; Sharma, S; Allen, TM; Altfeld, M; Jost, S
Published in: J Immunol
January 15, 2016

Multiple studies have shown correlates of immune activation with microbial translocation and plasma LPS during HIV infection. It is unclear whether this activation is due to LPS, residual viral replication, or both. Few studies have addressed the effects of persistent in vivo levels of LPS on specific immune functions in humans in the absence of chronic viral infection or pathological settings such as sepsis. We previously reported on a cohort of HIV-negative men with subclinical endotoxemia linked to alterations in CD4/CD8 T cell ratio and plasma cytokine levels. This HIV-negative cohort allowed us to assess cellular immune functions in the context of different subclinical plasma LPS levels ex vivo without confounding viral effects. By comparing two samples of differing plasma LPS levels from each individual, we now show that subclinical levels of plasma LPS in vivo significantly alter T cell proliferative capacity, monocyte cytokine release, and HLA-DR expression, and induce TLR cross-tolerance by decreased phosphorylation of MAPK pathway components. Using this human in vivo model of subclinical endotoxemia, we furthermore show that plasma LPS leads to constitutive activation of STAT1 through autocrine cytokine signaling, suggesting that subclinical endotoxemia in healthy individuals might lead to significant changes in immune function that have thus far not been appreciated.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

January 15, 2016

Volume

196

Issue

2

Start / End Page

668 / 677

Location

United States

Related Subject Headings

  • Young Adult
  • T-Lymphocytes
  • STAT1 Transcription Factor
  • Phosphorylation
  • Middle Aged
  • Male
  • Lipopolysaccharides
  • Immunology
  • Immunity, Innate
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Palmer, C. D., Romero-Tejeda, M., Sirignano, M., Sharma, S., Allen, T. M., Altfeld, M., & Jost, S. (2016). Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation. J Immunol, 196(2), 668–677. https://doi.org/10.4049/jimmunol.1501888
Palmer, Christine D., Marisol Romero-Tejeda, Michael Sirignano, Siddhartha Sharma, Todd M. Allen, Marcus Altfeld, and Stephanie Jost. “Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation.J Immunol 196, no. 2 (January 15, 2016): 668–77. https://doi.org/10.4049/jimmunol.1501888.
Palmer CD, Romero-Tejeda M, Sirignano M, Sharma S, Allen TM, Altfeld M, et al. Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation. J Immunol. 2016 Jan 15;196(2):668–77.
Palmer, Christine D., et al. “Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation.J Immunol, vol. 196, no. 2, Jan. 2016, pp. 668–77. Pubmed, doi:10.4049/jimmunol.1501888.
Palmer CD, Romero-Tejeda M, Sirignano M, Sharma S, Allen TM, Altfeld M, Jost S. Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation. J Immunol. 2016 Jan 15;196(2):668–677.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

January 15, 2016

Volume

196

Issue

2

Start / End Page

668 / 677

Location

United States

Related Subject Headings

  • Young Adult
  • T-Lymphocytes
  • STAT1 Transcription Factor
  • Phosphorylation
  • Middle Aged
  • Male
  • Lipopolysaccharides
  • Immunology
  • Immunity, Innate
  • Humans