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Disruption of granulocyte macrophage‐colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection
Author(s) -
GonzalezJuarrero Mercedes,
Hattle Jessica M.,
Izzo Angelo,
JunqueiraKipnis Ana Paula,
Shim Tae S.,
Trapnell Bruce C.,
Cooper Andrea M.,
Orme Ian M.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1204723
Subject(s) - biology , immunology , granulocyte macrophage colony stimulating factor , chemokine , cytokine , macrophage , tumor necrosis factor alpha , macrophage inflammatory protein , mycobacterium tuberculosis , tuberculosis , inflammation , medicine , pathology , biochemistry , in vitro
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 α (TNF‐α) nor the chemokines, regulated on activation, normal T expressed and secreted (RANTES), macrophage‐inflammatory protein‐1β (MIP‐1β), MIP‐1α, 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‐α and interferon‐γ in the lungs. However, GM+ mice succumb to infection between 60 and 90 days post‐challenge, as they are unable to develop a normal granulomatous 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‐1β. 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.