Relative levels of M-CSF and GM-CSF influence the specific generation of macrophage populations during infection with Mycobacterium tuberculosis.
Members of the CSF cytokine family play important roles in macrophage recruitment and activation. However, the role of M-CSF in pulmonary infection with Mycobacterium tuberculosis is not clear. In this study, we show the lungs of mice infected with M. tuberculosis displayed a progressive decrease in M-CSF in contrast to increasing levels of GM-CSF. Restoring pulmonary M-CSF levels during infection resulted in a significant decrease in the presence of foamy macrophages and increased expression of CCR7 and MHC class II, specifically on alveolar macrophages. In response to M-CSF, alveolar macrophages also increased their T cell-stimulating capacity and expression of DEC-205. These studies show that the levels of expression of M-CSF and GM-CSF participate in the progression of macrophages into foamy cells and that these cytokines are important factors in the differentiation and regulation of expression of dendritic cell-associated markers on alveolar macrophages. In addition, these studies demonstrate that M-CSF may have a role in the adaptive immune response to infection with M. tuberculosis.
Higgins
David M
DM
Department of Microbiology, Immunology and Pathology, Mycobacteria Research Laboratories, Colorado State University, Fort Collins, CO 80523, USA.
Sanchez-Campillo
Joaquin
J
Rosas-Taraco
Adrian G
AG
Higgins
Jonathan R
JR
Lee
Eric J
EJ
Orme
Ian M
IM
Gonzalez-Juarrero
Mercedes
M
D000818:Animals; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D002478:Cells, Cultured; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010641:Phenotype; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D000949:Histocompatibility Antigens Class II; D016212:Transforming Growth Factor beta; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor