| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Division of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine,
Children’s Hospital of Pittsburgh, Division of Pulmonology, Department of Pediatrics,
Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA;
Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada; and
¶ Fred Hutchinson Cancer Research Center, Seattle, WA
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-1β and IL-17 also individually induce lipocalin 2. Mucosal administration of IL-1β 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work is supported by grants from the National Institutes of Health, K08 HL089189-01 (to Y.R.C.) and R01HL079142, P30DK072506, and 5P50HL084932 (J.K.K.).
2 Address correspondence and reprint requests to Dr. Jay K. Kolls at the current address: Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, 530 45th Street, Pittsburgh, PA 15201. E-mail address: jay.kolls{at}chp.edu
3 Abbreviations used in this paper: KP, Klebsiella pneumoniae; KO, knockout; CCSP, Clara cell secretory protein; HBE, human bronchial epithelium; lcn2/Lcn2, lipocalin 2; NHBE, normal human bronchial epithelial cell; MLE, mouse lung epithelial cell; i.t., intratracheal; MMP-9, matrix metalloproteinase 9.
Related articles in The JI:
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
