Lipocalin 2 Is Required for Pulmonary Host Defense against Klebsiella Infection

Citations Over TimeTop 1% of 2009 papers

Abstract

Antimicrobial proteins comprise a significant component of the acute innate immune response to infection. They are induced by pattern recognition receptors as well as by cytokines of the innate and adaptive immune pathways and play important roles in infection control and immunomodulatory homeostasis. Lipocalin 2 (siderocalin, NGAL, 24p3), a siderophore-binding antimicrobial protein, is critical for control of systemic infection with Escherichia coli; however, its role in mucosal immunity in the respiratory tract is unknown. In this study, we found that lipocalin 2 is rapidly and robustly induced by Klebsiella pneumoniae infection and is TLR4 dependent. IL-1beta and IL-17 also individually induce lipocalin 2. Mucosal administration of IL-1beta alone could reconstitute the lipocalin 2 deficiency in TLR4 knockout animals and rescue them from infection. Lipocalin 2-deficient animals have impaired lung bacterial clearance in this model and mucosal reconstitution of lipocalin 2 protein in these animals resulted in rescue of this phenotype. We conclude that lipocalin 2 is a crucial component of mucosal immune defense against pulmonary infection with K. pneumoniae.

Related Papers

• → Human neutrophil gelatinase-associated lipocalin and homologous proteins in rat and mouse(2000)365 cited
• → <p>iTRAQ-Based Proteomics Reveals Potential Anti-Virulence Targets for ESBL-Producing <em>Klebsiella pneumoniae</em></p>(2020)11 cited
• → Lipocalin allergens(2001)40 cited
• → A FUNCTIONAL APPROACH ON NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN (NGAL) - LIPOCALIN FAMILY(2013)
• → Lipocalin 2 (LCN2)-deficient mice are more prone to hepatic steatosis: LCN2 and mitochondrial and peroxisomal integrity(2016)