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Suppression of TLR2-Induced IL-12, Reactive Oxygen Species, and Inducible Nitric Oxide Synthase Expression byMycobacterium tuberculosisAntigens Expressed inside Macrophages during the Course of Infection
- Source :
- The Journal of Immunology. 184:5444-5455
- Publication Year :
- 2010
- Publisher :
- The American Association of Immunologists, 2010.
-
Abstract
- We report the enrichment of and immune responses mediated by genes expressed by Mycobacterium tuberculosis inside macrophages as a function of time. Results indicate that M. tuberculosis expresses different genes at different times postinfection. Genes expressed early (day 1) following infection enhance M. tuberculosis-mediated activation of dendritic cells (DCs), whereas genes expressed later (day 5) in the infection prevent DC activation. However, all genes downmodulated MHC class I and II expression on infected macrophages, thus compromising their ability to interact with Ag-specific T cells. Day-1 and -5 genes downmodulated proinflammatory cytokine production from DCs, thus impairing signal 3 during DC–T cell cognate interactions. Consequently, T cells activated by Ag-experienced DCs secreted low levels of IFN-γ and IL-17 but maintained high IL-10 secretion, thus inducing suppressor responses. Further characterization revealed that day-1 and -5 genes increased TLR2-induced expression of suppressors of cytokine signaling 1 from DCs and downmodulated IL-12 expression. In addition, day-1 and -5 genes prevented the generation of reactive oxygen species in DCs. In contrast, although day-5 genes increased TLR2-mediated suppressors of cytokine signaling 1 expression in macrophages, day-1 genes downmodulated the expression of inducible NO synthase 2. Similar downregulation of immune responses was observed upon exogenous stimulation with day-1 or -5 Ags. Finally, day-1 and -5 genes promoted enhanced survival of M. tuberculosis inside DCs and macrophages. These results indicate that M. tuberculosis genes, expressed inside infected macrophages as a function of time, collectively suppress protective immune responses by using multiple and complementary mechanisms.
- Subjects :
- Time Factors
medicine.medical_treatment
Immunology
Cell
Nitric Oxide Synthase Type II
Proinflammatory cytokine
Mycobacterium tuberculosis
Mice
Immune system
Cell Line, Tumor
MHC class I
Immune Tolerance
medicine
Animals
Humans
Immunology and Allergy
Tuberculosis, Pulmonary
Antigens, Bacterial
Mice, Inbred BALB C
biology
Gene Expression Profiling
Macrophages
biology.organism_classification
Interleukin-12
Toll-Like Receptor 2
Cell biology
TLR2
Cytokine
medicine.anatomical_structure
Macrophages, Peritoneal
biology.protein
Interleukin 12
Female
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 184
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....d5c6377a445e3b7e651ea80517a3066e