TY - JOUR
T1 - Mycobacterium tuberculosis induces differential cytokine production from dendritic cells and macrophages with divergent effects on naive T cell polarization
AU - Hickman, Somia Perdow
AU - Chan, John
AU - Salgame, Padmini
PY - 2002/5/1
Y1 - 2002/5/1
N2 - Th1-mediated cellular responses are important for protection in tuberculosis. However, the mechanisms and APC types responsible for initiating Th1 responses are not well understood. These studies show that macrophages and dendritic cells, albeit both being APC, respond differently following Mycobacterium tuberculosis infection and thereby have different consequences for the development of naive T cells. We report that M. tuberculosis-infected dendritic cells bias the polarization of OVA peptide-specific naive transgenic T cells to the Th1 phenotype, and, in contrast, in the presence of infected macrophages naive T cells do not develop a Th1 phenotype. Comparison of the cytokine profile expressed by the infected dendritic cells and macrophages revealed several differences, the most striking being that infected macrophages did not express the Th1-promoting cytokine IL-12. These studies also show that IL-10 is responsible for the failure of IL-12 production by M. tuberculosis-infected macrophages, and that the effects of IL-10 can be overcome by IFN-γ priming. We speculate that the observed difference in response of the two APC types to M. tuberculosis infection may be a reflection of their respective roles in immune initiation and granuloma regulation.
AB - Th1-mediated cellular responses are important for protection in tuberculosis. However, the mechanisms and APC types responsible for initiating Th1 responses are not well understood. These studies show that macrophages and dendritic cells, albeit both being APC, respond differently following Mycobacterium tuberculosis infection and thereby have different consequences for the development of naive T cells. We report that M. tuberculosis-infected dendritic cells bias the polarization of OVA peptide-specific naive transgenic T cells to the Th1 phenotype, and, in contrast, in the presence of infected macrophages naive T cells do not develop a Th1 phenotype. Comparison of the cytokine profile expressed by the infected dendritic cells and macrophages revealed several differences, the most striking being that infected macrophages did not express the Th1-promoting cytokine IL-12. These studies also show that IL-10 is responsible for the failure of IL-12 production by M. tuberculosis-infected macrophages, and that the effects of IL-10 can be overcome by IFN-γ priming. We speculate that the observed difference in response of the two APC types to M. tuberculosis infection may be a reflection of their respective roles in immune initiation and granuloma regulation.
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U2 - 10.4049/jimmunol.168.9.4636
DO - 10.4049/jimmunol.168.9.4636
M3 - Article
C2 - 11971012
AN - SCOPUS:0036569397
SN - 0022-1767
VL - 168
SP - 4636
EP - 4642
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -