title: Arginase 1 activity worsens lung-protective immunity against Streptococcus pneumoniae infection.
abstract: Type 2 helper cell (Th2) dominated chronic lung diseases such as asthma are characterized by an increased risk for bacterial lung infections. However, the underlying mechanisms are poorly defined. Arginase 1 (Arg1) has been suggested to play an important role in the pathophysiology of asthma, and is rapidly induced in lung macrophages by Th2 cytokines, thereby limiting macrophage-derived antimicrobial nitric oxide (NO) production. Here we examined the effect of Th2 cytokine induced upregulation or lung myeloid cell specific conditional knockdown of Arg1 on lung resistance against Streptococcus pneumoniae (Spn) in mice. Lung macrophages responded with a profound induction of Arg1 mRNA and protein to treatment with IL-13 both in vitro and in vivo. IL-13-induced Arg1 activity in the lungs of mice led to significantly attenuated lung-protective immunity against Spn, while conditional Arg1 knockdown had no effect on lung-protective immunity against Spn. Collectively, the data show that Th2 cytokine induced increased Arg1 activity worsens lung-protective immunity against Spn, and interventions to block Th2 cytokine induced lung Arg1 activity may thus be a novel immunomodulatory strategy to lower the risk of bacterial infections in asthmatic patients.
authors: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
authors: Sarah
authors: S
authors: Knippenberg
authors: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
authors: Christina
authors: C
authors: Brumshagen
authors: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
authors: Franziska
authors: F
authors: Aschenbrenner
authors: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research BREATH, Hannover, Germany.
authors: Tobias
authors: T
authors: Welte
authors: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.|German Centre for Lung Research BREATH, Hannover, Germany.
authors: Ulrich A
authors: UA
authors: Maus
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; C544448:Arg1 protein, mouse; D001119:Arginase
keywords: Alternative macrophage activation; Arg1; IL-13; Inflammation; Lung