Arginase 1 activity worsens lung protective immunity against Streptococcus pneumoniae infection.

Eur J Immunol. 2015 Mar 18. doi: 10.1002/eji.201445419. [Epub ahead of print]

Arginase 1 activity worsens lung protective immunity against Streptococcus pneumoniae infection.

Knippenberg S1, Brumshagen C, Aschenbrenner F, Welte T, Maus UA.

Abstract

Type 2 helper cell (Th2) dominated chronic lung diseases like 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. Interleukin 13-induced Arg1 activity in the lungs of mice led to significantly attenuated lung protective immunity against Spn, while conditional Arg1 knock-down 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. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS:

Alternative macrophage activation; Arg1; IL-13; Inflammation; Lung

PMID: 25789453 [PubMed - as supplied by publisher]