Severe Tuberculosis Induces Unbalanced Up‐Regulation of Gene Networks and Overexpression ofIL‐22, MIP‐1α, CCL27, IP‐10, CCR4, CCR5, CXCR3, PD1, PDL2, IL‐3, IFN‐β, TIM1,andTLR2but Low Antigen‐Specific Cellular Responses
| Autor: | Norman L. Letvin, Robert E. Hunt, Yun Shen, William R. Jacobs, Dan Huang, Crystal Y. Chen, George Du, Barton F. Haynes, James E. Estep, Richard Wang, Zheng W. Chen, Ling Shen, Liyou Qiu |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_treatment
T cell Receptors Cell Surface Biology Article Proinflammatory cytokine Interleukin 22 Immune system Antigen medicine Animals Tuberculosis Immunology and Allergy Gene Regulatory Networks Receptor Lung Immunity Cellular Mycobacterium Infections Macaca mulatta Up-Regulation TLR2 Infectious Diseases Cytokine medicine.anatomical_structure Immunology Leukocytes Mononuclear Cancer research Cytokines |
| Zdroj: | The Journal of Infectious Diseases. 198:1514-1519 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1086/592448 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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