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Original Article

^a Louisiana State University Health Sciences Gene Therapy Program, Section of Pulmonary/Critical Care Medicine, New Orleans, LA 70112
^b Immunex Corporation, Seattle, WA 98101
LSUHSC Gene Therapy Program, CSRB 601, 533 Bolivar St., New Orleans, LA 70112.504-568-8500504-568-6152

jkolls{at}lshsc.edu

Bacterial pneumonia is an increasing complication of HIV infection and inversely correlates with the CD4⁺ lymphocyte count. Interleukin (IL)-17 is a cytokine produced principally by CD4⁺ T cells, which induces granulopoiesis via granulocyte colony-stimulating factor (G-CSF) production and induces CXC chemokines. We hypothesized that IL-17 receptor (IL-17R) signaling is critical for G-CSF and CXC chemokine production and lung host defenses. To test this, we used a model of Klebsiella pneumoniae lung infection in mice genetically deficient in IL-17R or in mice overexpressing a soluble IL-17R. IL-17R–deficient mice were exquisitely sensitive to intranasal K. pneumoniae with 100% mortality after 48 h compared with only 40% mortality in controls. IL-17R knockout (KO) mice displayed a significant delay in neutrophil recruitment into the alveolar space, and had greater dissemination of K. pneumoniae compared with control mice. This defect was associated with a significant reduction in steady-state levels of G-CSF and macrophage inflammatory protein (MIP)-2 mRNA and protein in the lung in response to the K. pneumoniae challenge in IL-17R KO mice. Thus, IL-17R signaling is critical for optimal production of G-CSF and MIP-2 and local control of pulmonary K. pneumoniae infection. These data support impaired IL-17R signaling as a potential mechanism by which deficiency of CD4 lymphocytes predisposes to bacterial pneumonia.

Key Words: IL-17 • T lymphocyte • granulocyte-colony stimulating factor • Klebsiella pneumoniae • chemokine

© 2001 The Rockefeller University Press

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This article has been cited by other articles:

• Fujisawa, T., Velichko, S., Thai, P., Hung, L.-Y., Huang, F., Wu, R. (2009). Regulation of Airway MUC5AC Expression by IL-1{beta} and IL-17A; the NF-{kappa}B Paradigm. J. Immunol. 183: 6236-6243 [Abstract] [Full Text]  

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