COX-2 Inhibition Reduces Brucella Bacterial Burden in Draining Lymph Nodes
| Autor: | Jean-Pierre Gorvel, Aurélie Gagnaire, Jean-Louis Mege, Laurent Gorvel, Kristine von Bargen, Alexia Papadopoulos |
|---|---|
| Přispěvatelé: | Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), VAFFIDES, Chantal, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), INSB-INSB-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Microbiology (medical) [SDV.IMM] Life Sciences [q-bio]/Immunology lcsh:QR1-502 Prostaglandin Brucella Microbiology lcsh:Microbiology prostaglandins 03 medical and health sciences chemistry.chemical_compound Immune system medicine intradermal infection biology Intracellular parasite Dendritic Cells COX-2 biology.organism_classification 3. Good health Interleukin 10 030104 developmental biology medicine.anatomical_structure chemistry Cervical lymph nodes denditric cells Immunology [SDV.IMM]Life Sciences [q-bio]/Immunology Arachidonic acid Lymph |
| Zdroj: | Frontiers in Microbiology Frontiers in Microbiology, 2016, 7, ⟨10.3389/fmicb.2016.01987⟩ Frontiers in Microbiology, Vol 7 (2016) Frontiers in Microbiology, Frontiers Media, 2016, 7, ⟨10.3389/fmicb.2016.01987⟩ |
| ISSN: | 1664-302X |
| DOI: | 10.3389/fmicb.2016.01987⟩ |
| Popis: | International audience; Brucella is a Gram-negative facultative intracellular bacterium responsible for a chronic disease known as brucellosis, the most widespread re-emerging zoonosis worldwide. Establishment of a Th1-mediated immune response characterized by the production of IL-12 and IFN gamma is essential to control the disease. Leukotrienes derived from arachidonic acid (AA) metabolism are known to negatively regulate a protective Th1 immune response against bacterial infections. Here, using genomics approaches we demonstrate that Brucella abortus strongly stimulates the prostaglandin (PG) pathway in dendritic cells (DC). We also show an induction of AA production by infected cells. This correlates with the expression of Ptgs2, a gene encoding the downstream cyclooxygenase-2 (COX-2) enzyme in infected DC. By comparing different infection routes (oral, intradermal, intranasal and conjunctival), we identified the intradermal inoculation route as the more potent in inducing Ptgs2 expression but also in inducing a local inflammatory response in the draining cervical lymph nodes (CLN). NS-398, a specific inhibitor of COX-2 enzymatic activity decreased B. melitensis burden in the CLN after intradermal infection. This effect was accompanied by a decrease of II10 and a concomitant increase of Ifng expression. Altogether, these results suggest that Brucella has evolved to take advantage of the PG pathway in the harsh environment of the CLN in order to persist and subvert immune responses. This work also proposes that novel strategies to control brucellosis may include the use of COX-2 inhibitors. |
| Databáze: | OpenAIRE |
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