Lipocalin 2 is required for pulmonary host defense against Klebsiella infection

YR Chan, JS Liu, DA Pociask, M Zheng… - The Journal of …, 2009 - journals.aai.org
YR Chan, JS Liu, DA Pociask, M Zheng, TA Mietzner, T Berger, TW Mak, MC Clifton
The Journal of Immunology, 2009journals.aai.org
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 …
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-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.
journals.aai.org