HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print March 14, 2005

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.1204723v1 77/6/914    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gonzalez-Juarrero, M. Articles by Orme, I. M. Search for Related Content PubMed PubMed Citation Articles by Gonzalez-Juarrero, M. Articles by Orme, I. M.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1204723

Received for publication December 13, 2004.
Revised January 25, 2005.
Accepted for publication February 3, 2005.

Article

Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection

Mercedes Gonzalez-Juarrero ^*@, Jessica M. Hattle ^*, Angelo Izzo ^*, Ana Paula Junquiera-Kipnis ^*, Tae S. Shim ^*, Bruce C. Trapnell , Andrea M. Cooper , and Ian M. Orme ^*

*Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins; Division of Pulmonary Biology, Children’s Hospital Research Foundation, University of Cincinnati, Ohio; and Trudeau Institute, Saranac Lake, New York

^@ To whom correspondence should be addressed. E-mail: malba{at}lamar.colostate.edu.

	Abstract

Mice lacking expression of granulocyte macrophage-colony stimulating factor knockout (GM-CSF KO) are unable to contain Mycobacterium 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 (TNF-) nor the chemokines, regulated on activation, normal T expressed and secreted (RANTES), macrophage-inflammatory protein-1 (MIP-1), MIP-1, 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- and interferon- 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-1. 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.

Key Words: GM-CSF • cytokines • chemokines • granuloma

This article has been cited by other articles:

				D. M. Higgins, J. Sanchez-Campillo, A. G. Rosas-Taraco, J. R. Higgins, E. J. Lee, I. M. Orme, and M. Gonzalez-Juarrero Relative Levels of M-CSF and GM-CSF Influence the Specific Generation of Macrophage Populations during Infection with Mycobacterium tuberculosis J. Immunol., April 1, 2008; 180(7): 4892 - 4900. [Abstract] [Full Text] [PDF]

				A. A. Ryan, T. M. Wozniak, E. Shklovskaya, M. A. O'Donnell, B. Fazekas de St. Groth, W. J. Britton, and J. A. Triccas Improved Protection against Disseminated Tuberculosis by Mycobacterium bovis Bacillus Calmette-Guerin Secreting Murine GM-CSF Is Associated with Expansion and Activation of APCs J. Immunol., December 15, 2007; 179(12): 8418 - 8424. [Abstract] [Full Text] [PDF]

				D. Ordway, D. M. Higgins, J. Sanchez-Campillo, J. S. Spencer, M. Henao-Tamayo, M. Harton, I. M. Orme, and M. Gonzalez Juarrero XCL1 (lymphotactin) chemokine produced by activated CD8 T cells during the chronic stage of infection with Mycobacterium tuberculosis negatively affects production of IFN-{gamma} by CD4 T cells and participates in granuloma stability J. Leukoc. Biol., November 1, 2007; 82(5): 1221 - 1229. [Abstract] [Full Text] [PDF]

				G.-H. Chen, M. A. Olszewski, R. A. McDonald, J. C. Wells, R. Paine III, G. B. Huffnagle, and G. B. Toews Role of Granulocyte Macrophage Colony-Stimulating Factor in Host Defense Against Pulmonary Cryptococcus neoformans Infection during Murine Allergic Bronchopulmonary Mycosis Am. J. Pathol., March 1, 2007; 170(3): 1028 - 1040. [Abstract] [Full Text] [PDF]

				B. Carey, M. K. Staudt, D. Bonaminio, J. C. M. van der Loo, and B. C. Trapnell PU.1 Redirects Adenovirus to Lysosomes in Alveolar Macrophages, Uncoupling Internalization from Infection J. Immunol., February 15, 2007; 178(4): 2440 - 2447. [Abstract] [Full Text] [PDF]

				K. Uchida, D. C. Beck, T. Yamamoto, P.-Y. Berclaz, S. Abe, M. K. Staudt, B. C. Carey, M.-D. Filippi, S. E. Wert, L. A. Denson, et al. GM-CSF Autoantibodies and Neutrophil Dysfunction in Pulmonary Alveolar Proteinosis N. Engl. J. Med., February 8, 2007; 356(6): 567 - 579. [Abstract] [Full Text] [PDF]

				P.-Y. Berclaz, B. Carey, M.-D. Fillipi, K. Wernke-Dollries, N. Geraci, S. Cush, T. Richardson, J. Kitzmiller, M. O'Connor, C. Hermoyian, et al. GM-CSF Regulates a PU.1-Dependent Transcriptional Program Determining the Pulmonary Response to LPS Am. J. Respir. Cell Mol. Biol., January 1, 2007; 36(1): 114 - 121. [Abstract] [Full Text] [PDF]

				T. C. Thacker, M. V. Palmer, and W. R. Waters Correlation of Cytokine Gene Expression with Pathology in White-Tailed Deer (Odocoileus virginianus) Infected with Mycobacterium bovis Clin. Vaccine Immunol., June 1, 2006; 13(6): 640 - 647. [Abstract] [Full Text] [PDF]

				D. Ordway, M. Harton, M. Henao-Tamayo, R. Montoya, I. M. Orme, and M. Gonzalez-Juarrero Enhanced Macrophage Activity in Granulomatous Lesions of Immune Mice Challenged with Mycobacterium tuberculosis. J. Immunol., April 15, 2006; 176(8): 4931 - 4939. [Abstract] [Full Text] [PDF]

				J. A. Tree, M. J. Elmore, S. Javed, A. Williams, and P. D. Marsh Development of a Guinea Pig Immune Response-Related Microarray and Its Use To Define the Host Response following Mycobacterium bovis BCG Vaccination Infect. Immun., February 1, 2006; 74(2): 1436 - 1441. [Abstract] [Full Text] [PDF]