Abstract |
Recognition of Mycobacterium tuberculosis by the innate immune system is essential in the development of an adaptive immune response. Mycobacterial cell wall components activate macrophages through Toll-like receptor (TLR) 2, suggesting that this innate immune receptor plays a role in the host response to M. tuberculosis infection. After aerosol infection with either 100 or 500 live mycobacteria, TLR2-deficient mice display reduced bacterial clearance, a defective granulomatous response, and develop chronic pneumonia. Analysis of pulmonary immune responses in TLR2-deficient mice after 500 mycobacterial aerosol challenge showed increased levels of interferon-gamma, tumor necrosis factor-alpha, and interleukin-12p40 as well as increased numbers of CD4(+) and CD8(+) cells. Furthermore, TLR2-deficient mice mounted elevated Ag-specific type 1 T-cell responses that were not protective because all deficient mice succumb to infection within 5 months. Taken together, the data suggests that TLR2 may function as a regulator of inflammation, and in its absence an exaggerated immune inflammatory response develops.
|
Authors | Michael B Drennan, Delphine Nicolle, Valerie J F Quesniaux, Muazzam Jacobs, Nasiema Allie, Joseph Mpagi, Cécile Frémond, Hermann Wagner, Carsten Kirschning, Bernhard Ryffel |
Journal | The American journal of pathology
(Am J Pathol)
Vol. 164
Issue 1
Pg. 49-57
(Jan 2004)
ISSN: 0002-9440 [Print] United States |
PMID | 14695318
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Cytokines
- Membrane Glycoproteins
- Receptors, Cell Surface
- Toll-Like Receptor 2
- Toll-Like Receptors
|
Topics |
- Animals
- CD4-Positive T-Lymphocytes
(immunology, microbiology)
- Cytokines
(immunology)
- Lung
(immunology, microbiology, pathology)
- Lymphocyte Activation
(immunology)
- Macrophages, Peritoneal
(immunology, microbiology)
- Membrane Glycoproteins
(deficiency, immunology)
- Mice
- Mycobacterium tuberculosis
- Receptors, Cell Surface
(deficiency, immunology)
- Toll-Like Receptor 2
- Toll-Like Receptors
- Tuberculosis
(genetics, immunology)
|