Back to Search
Start Over
Aryl Hydrocarbon Receptor-Signaling Regulates Early Leishmania major-Induced Cytokine Expression
- Source :
- Frontiers in Immunology, Frontiers in Immunology, Vol 10 (2019)
- Publication Year :
- 2019
- Publisher :
- Frontiers Media SA, 2019.
-
Abstract
- The early inflammatory skin micromilieu affects resistance in experimental infection with Leishmania major. We pursue the concept that macrophages, which take up parasites during early infection, exert decisive influence on the inflammatory micromilieu after infection. In order to analyze their distinctive potential, we identified differentially regulated genes of murine granuloma macrophages (GMΦ) from resistant and susceptible mice after their infection with metacyclic Leishmania major. We found induction of several cytokines in GMΦ from both strains and a stronger upregulation of the transcription factor aryl hydrocarbon receptor (AhR) in GMΦ from resistant mice. Using both an AhR agonist and antagonist we demonstrated that AhR is involved in Leishmania-induced production of TNF in macrophages. In vivo, single local injection of an AhR agonist in early lesions of susceptible mice caused an increased induction of Tnf and other cytokines in the skin. Importantly, local agonist treatment led to a reduction of disease severity, reduced parasite loads and a weaker Th2 response. Our results demonstrate that local activation of AhR has a beneficial effect in experimental leishmaniasis.
- Subjects :
- lcsh:Immunologic diseases. Allergy
0301 basic medicine
Agonist
medicine.drug_class
Immunology
Gene Expression
Leishmaniasis, Cutaneous
Monocytes
Host-Parasite Interactions
Mice
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
In vivo
epidermis
medicine
Animals
Humans
Immunology and Allergy
Leishmania major
leishmaniasis
Transcription factor
Original Research
skin infection
biology
Epidermis (botany)
Macrophages
AhR
Aryl hydrocarbon receptor
biology.organism_classification
Disease Models, Animal
030104 developmental biology
Receptors, Aryl Hydrocarbon
biology.protein
Cytokines
Female
Tumor necrosis factor alpha
lcsh:RC581-607
Signal Transduction
030215 immunology
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....1d353b05b173b5fdd4576a99837d5745