title: Lipocalin 2 is required for pulmonary host defense against Klebsiella infection.
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.
authors.affiliation: Department of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Yvonne R
authors.initials: YR
authors.lastname: Chan
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Liu
authors.forename: Derek A
authors.initials: DA
authors.lastname: Pociask
authors.forename: Mingquan
authors.initials: M
authors.lastname: Zheng
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Mietzner
authors.forename: Thorsten
authors.initials: T
authors.lastname: Berger
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Clifton
authors.forename: Roland K
authors.initials: RK
authors.lastname: Strong
authors.forename: Prabir
authors.initials: P
authors.lastname: Ray
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls