TNF Influences Chemokine Expression of Macrophages In Vitro and That of CD11b+ Cells In Vivo during Mycobacterium tuberculosis Infection
| Autor: | Philana Ling Lin, Alvin Jones, David J. Yankura, JoAnne L. Flynn, Holly M. Scott Algood, John Chan |
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| Rok vydání: | 2004 |
| Předmět: |
Immunology
Biology CCL7 Chemokine CXCL9 Mice Animals Tuberculosis Immunology and Allergy CCL17 CCL13 CX3CL1 Lung Cells Cultured In Situ Hybridization CXCL16 CD11b Antigen Tumor Necrosis Factor-alpha Macrophages respiratory system Chemokine CXCL10 Mice Inbred C57BL CXCL2 Intercellular Signaling Peptides and Proteins Female Disease Susceptibility Chemokines Chemokines CXC CCL23 CCL21 |
| Zdroj: | The Journal of Immunology. 172:6846-6857 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.172.11.6846 |
| Popis: | Granulomas, focal accumulations of immune cells, form in the lung during Mycobacterium tuberculosis infection. Chemokines, chemotactic cytokines, are logical candidates for inducing migration of T lymphocytes and monocytes to and within the lung. TNF influences chemokine expression in some models. TNF-deficient mice infected with M. tuberculosis are highly susceptible to disease, and granuloma formation is inhibited. Through in vitro assays, we demonstrate that neutralization of TNF in M. tuberculosis-infected macrophages led to a reduction in many inflammatory chemokines, such as C-C chemokine ligand 5, CXC ligand 9 (CXCL9), and CXCL10. In TNF-deficient mice, immune cells migrated to the lungs early after infection, but did not organize to form granulomas within the lung. Although chemokine expression, as measured in whole lung tissue, was not different, the expression of chemokines in the CD11b+ subset of cells isolated ex vivo from the lungs of TNF-deficient mice had reduced expression of C-C chemokine ligand 5, CXCL9, and CXCL10 at early time points after TNF neutralization. Local expression of CXCR3-binding chemokines within the lungs, as determined by in situ hybridization, was also affected by TNF. Therefore, TNF affects the expression of chemokines by macrophages in vitro and CD11b+ cells in vivo, which probably influences the local chemokine gradients and granuloma formation. |
| Databáze: | OpenAIRE |
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