CD154 activates macrophage antimicrobial activity in the absence of IFN-gamma through a TNF-alpha-dependent mechanism

Protection against certain intracellular pathogens can take place in the absence of IFN-gamma through mechanisms dependent on TNF-alpha. In this regard, patients with partial defect in IFN-gamma receptor 1 are not susceptible to toxoplasmosis. Thus, we used a model of Toxoplasma gondii infection to...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2003-12, Vol.171 (12), p.6750-6756
Main Authors: Andrade, Rosa M, Wessendarp, Matthew, Subauste, Carlos S
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - physiology
Animals
CD40 Ligand - physiology
Cells, Cultured
Dose-Response Relationship, Immunologic
Humans
Interferon-gamma - deficiency
Interferon-gamma - physiology
Macrophage Activation - immunology
Macrophages - immunology
Macrophages - metabolism
Macrophages - parasitology
Monocytes - immunology
Monocytes - parasitology
Recombinant Proteins - pharmacology
Signal Transduction - immunology
Toxoplasma - growth & development
Toxoplasma - immunology
Tumor Necrosis Factor-alpha - metabolism
Tumor Necrosis Factor-alpha - physiology
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Summary:Protection against certain intracellular pathogens can take place in the absence of IFN-gamma through mechanisms dependent on TNF-alpha. In this regard, patients with partial defect in IFN-gamma receptor 1 are not susceptible to toxoplasmosis. Thus, we used a model of Toxoplasma gondii infection to investigate whether CD154 modulates IFN-gamma-independent mechanisms of host protection. Human monocyte-derived macrophages treated with recombinant CD154 exhibited increased anti-T. gondii activity. The number of tachyzoites per 100 macrophages at 20 h postinfection was lower in CD154-treated macrophages compared with controls. This was accompanied by a decrease in the percentage of infected cells in CD154-treated macrophages at 20 h compared with 1 h postinfection. CD154-bearing cells also induced antimicrobial activity in T. gondii-infected macrophages. CD154 enhanced macrophage anti-T. gondii activity independently of IFN-gamma. TNF-alpha mediated the effects of CD154 on macrophage anti-T. gondii activity. CD154 increased TNF-alpha production by T. gondii-infected macrophages, and neutralization of TNF-alpha inhibited the effect of CD154 on macrophage anti-T. gondii activity. These results demonstrate that CD154 triggers TNF-alpha-dependent antimicrobial activity in macrophages and suggest that CD154 regulates the mechanisms of host protection that take place when IFN-gamma signaling is deficient.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.171.12.6750