Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1alpha, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-beta, TIM1, and TLR2 but low antigen-specific cellular responses.

Published

Journal Article

The immune mechanisms by which early host-mycobacterium interaction leads to the development of severe tuberculosis (TB) remain poorly characterized in humans. Here, we demonstrate that severe TB in juvenile rhesus monkeys down-regulated many genes in the blood but up-regulated selected genes constituting gene networks of Th17 and Th1 responses, T cell activation and migration, and inflammation and chemoattractants in the pulmonary and lymphoid compartments. Overexpression (450-2740-fold) of 13 genes encoding inflammatory cytokines and receptors (IL-22, CCL27, MIP-1alpha, IP-10, CCR4, CCR5, and CXCR3), immune dysfunctional receptors and ligands (PD1 and PDL2), and immune activation elements (IL-3, IFN-beta, TIM1, and TLR2) was seen in tissues, with low antigen-specific cellular responses. Thus, severe TB in macaques features unbalanced up-regulation of immune-gene networks without proportional increases in antigen-specific cellular responses.

Full Text

Duke Authors

Cited Authors

  • Qiu, L; Huang, D; Chen, CY; Wang, R; Shen, L; Shen, Y; Hunt, R; Estep, J; Haynes, BF; Jacobs, WR; Letvin, N; Du, G; Chen, ZW

Published Date

  • November 2008

Published In

Volume / Issue

  • 198 / 10

Start / End Page

  • 1514 - 1519

PubMed ID

  • 18811584

Pubmed Central ID

  • 18811584

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

International Standard Serial Number (ISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1086/592448

Language

  • eng