Back to Search
Start Over
An oily, sustained counter-regulatory response to TB
- Publication Year :
- 2005
- Publisher :
- American Society for Clinical Investigation, 2005.
-
Abstract
- Th1 type cytokine responses are critical in the control of Mycobacterium tuberculosis infection. Recent findings indicate that 5-lipoxygenase-dependent (5-LO-dependent) lipoxins regulate host IL-12 production in vivo. Here, we establish lipoxins as key chemical mediators in resistance to M. tuberculosis infection. High levels of lipoxin A4 (LXA4) were detected in sera from infected WT but not infected 5-LO-deficient mice. Moreover, lungs from M. tuberculosis-infected 5-lo-/- animals showed increased IL-12, IFN-gamma, and NO synthase 2 (NOS2) mRNA levels compared with the same tissues in WT mice. Similarly, splenocyte recall responses were enhanced in mycobacteria-infected 5-lo-/- versus WT mice. Importantly, bacterial burdens in 5-lo-/- lungs were significantly lower than those from WT mice, and this enhancement in the resistance of the 5-lo-/- animals to M. tuberculosis was completely prevented by administration of a stable LXA4 analog. Together our results demonstrate that lipoxins negatively regulate protective Th1 responses against mycobacterial infection in vivo and suggest that the inhibition of lipoxin biosynthesis could serve as a strategy for enhancing host resistance to M. tuberculosis.
- Subjects :
- Tuberculosis
Inflammation
Pathogenesis
Mycobacterium tuberculosis
chemistry.chemical_compound
Mice
Immune system
Medicine
Humans
Animals
Lung
Tuberculosis, Pulmonary
Research Articles
Mice, Knockout
Lipoxin
Lipoxin synthesis
Arachidonate 5-Lipoxygenase
biology
business.industry
General Medicine
Lipid signaling
Th1 Cells
biology.organism_classification
medicine.disease
Lipoxins
chemistry
Immunology
Commentary
Cytokines
lipids (amino acids, peptides, and proteins)
medicine.symptom
Nitric Oxide Synthase
business
Spleen
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....9fa0cfe6419103bd2e52e2345c628762