
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.
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.
Duke Scholars
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Related Subject Headings
- Up-Regulation
- Tuberculosis
- Receptors, Cell Surface
- Mycobacterium Infections
- Microbiology
- Macaca mulatta
- Lung
- Leukocytes, Mononuclear
- Immunity, Cellular
- Gene Regulatory Networks
Citation

Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Up-Regulation
- Tuberculosis
- Receptors, Cell Surface
- Mycobacterium Infections
- Microbiology
- Macaca mulatta
- Lung
- Leukocytes, Mononuclear
- Immunity, Cellular
- Gene Regulatory Networks