期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 77, 期 6, 页码 914-922出版社
WILEY
DOI: 10.1189/jlb.1204723
关键词
GM-CSF; cytokines; chemokines; granuloma
资金
- NIAID NIH HHS [AI-40488, AI-44072] Funding Source: Medline
Mice lacking expression of granulocyte macrophage-colony stimulating factor (GM-CSF KO) are unable to contain Mycobacterium tuberculosis (M. tuberculosis) growth and succumb to infection by 35 days following pulmonary challenge. GM-CSF KO mice do not express normal levels of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) nor the chemokines, regulated on activation, normal T expressed and secreted (RANTES), macrophage-inflammatory protein-1 beta (MIP-1 beta), MIP-1 alpha, and lymphotactin, which are required for recruitment of lymphocytes and expression of a T helper cell type 1 (TH1) response within the lungs. In contrast, transgenic mice overexpressing GM-CSF in the lungs but with a lack of GM-CSF in other organs (GM+) are able to recruit lymphocytes and to express a TH1 response with production of TNF-alpha and interferon-gamma in the lungs. However, GM+ mice succumb to infection between 60 and 90 days post-challenge, as they are unable to develop a normal granulomatons response. Although GM+ mice are able to express the chemokine RANTES, they lack the ability to express other inflammatory chemokines such as lymphotactin and MIP-1 beta. We conclude that GM-CSF is essential to the recruitment of lymphocytes and expression of a TH1 response in the lung, to the generation of a normal mononuclear granuloma, and most importantly, to the containment of M. tuberculosis bacterial growth.
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