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

Liyou Qiu, Dan Huang, Crystal Y. Chen, Richard Wang, Ling Shen, Yun Shen, Robert Hunt, James Estep, Barton F. Haynes, William R. Jacobs, Norman L. Letvin, George Du, Zheng W. Chen

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

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 downregulated 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-1α, IP-10, CCR4, CCR5, and CXCR3), immune dysfunctional receptors and ligands (PD1 and PDL2), and immune activation elements (IL-3, IFN-β, 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.

Original languageEnglish (US)
Pages (from-to)1514-1519
Number of pages6
JournalJournal of Infectious Diseases
Volume198
Issue number10
DOIs
StatePublished - Nov 15 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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