| Autor: |
Villeret B; Laboratoire d'Excellence Inflamex, Institut National de la Santé et de la Recherche Medicale U1152, Physiopathologie et Épidémiologie des Maladies Respiratoires, Université de Paris-Cité, 75006 Paris, France., Ghinnagow R; Laboratoire d'Excellence Inflamex, Institut National de la Santé et de la Recherche Medicale U1152, Physiopathologie et Épidémiologie des Maladies Respiratoires, Université de Paris-Cité, 75006 Paris, France., Kheir S; Laboratoire d'Excellence Inflamex, Institut National de la Santé et de la Recherche Medicale U1152, Physiopathologie et Épidémiologie des Maladies Respiratoires, Université de Paris-Cité, 75006 Paris, France., Born-Bony M; Laboratoire d'Excellence Inflamex, Institut National de la Santé et de la Recherche Medicale U1152, Physiopathologie et Épidémiologie des Maladies Respiratoires, Université de Paris-Cité, 75006 Paris, France., Kolls JK; Center for Translational Research in Infection and Inflammation, Tulane School of Medicine, New Orleans, LA 70112, USA., Garcia-Verdugo I; Laboratoire d'Excellence Inflamex, Institut National de la Santé et de la Recherche Medicale U1152, Physiopathologie et Épidémiologie des Maladies Respiratoires, Université de Paris-Cité, 75006 Paris, France., Sallenave JM; Laboratoire d'Excellence Inflamex, Institut National de la Santé et de la Recherche Medicale U1152, Physiopathologie et Épidémiologie des Maladies Respiratoires, Université de Paris-Cité, 75006 Paris, France. |
| Abstrakt: |
Pseudomonas aeruginosa ( P.a ) is a pathogen causing significant morbidity and mortality, particularly in hospital patients undergoing ventilation and in individuals with cystic fibrosis. Although we and others have investigated mechanisms used by P.a to subvert innate immunity, relatively less is known about the potential strategies used by this bacterium to fight the adaptive immune system and, in particular, T cells. Here, using RAG KO (devoid of 'classical' αβ and γδ TCR T lymphocytes) and double RAG γC KO mice (devoid of T, NK and ILC cells), we demonstrate that the lymphocytic compartment is important to combat P.a (PAO1 strain). Indeed, we show that PAO1 load was increased in double RAG γC KO mice. In addition, we show that PAO1 down-regulates IL-23 and IL-22 protein accumulation in the lungs of infected mice while up-regulating their RNA production, thereby pointing towards a specific post-transcriptional regulatory mechanism not affecting other inflammatory mediators. Finally, we demonstrate that an adenovirus-mediated over-expression of IL-1, IL-23 and IL-7 induced lung neutrophil and lymphocytic influx and rescued mice against P.a -induced lethality in all WT, RAG γC KO and RAG γC KO RAG-deficient mice, suggesting that this regimen might be of value in 'locally immunosuppressed' individuals such as cystic fibrosis patients. |
