Requirement of Interleukin 17 Receptor Signaling for Lung Cxc Chemokine and Granulocyte Colony-Stimulating Factor Expression, Neutrophil Recruitment, and Host Defense

By P. Ye, F. H. Rodriguez, S. Kanaly, K. Stocking, J. Schurr, P. Schwarzenberger, P. Oliver, Weitao Huang, Ping Zhang, Jason Zhang and 6 more. Journal of Experimental Medicine, 2001

1,681 citations recorded by the source corpus.

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.

Subfields: Immunology, Oncology, Physiology

View Paper: https://www.semanticscholar.org/paper/a9b2b1f790518d3f4d8ad79c3c91800acfdf057b

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In Immunology

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In Oncology

1. C. Dong
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8. Y. Kanno

In Physiology

1. Wenjun Ouyang
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3. Yan Zheng
4. M. F. Gulen
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6. TA Wynn
7. S. Nakae

Citations in the corpus

• IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia (2008, background): “These mice do not mount a normal mucosal granulocyte colony–stimulating factor (G-CSF) response, which leads to defective granulopoiesis in response to the infectio”
• Cutting Edge: Interleukin 17 Signals through a Heteromeric Receptor Complex (2006, background): “129-Il17ra tm1Koll (IL-17RA / ) mice has been described previously (3).”
• TH17 cells in development: an updated view of their molecular identity and genetic programming (2008, background): “Similarly in vivo , IL-17RA-deficient mice had impaired host defence against mycobacterial infection due to a significant decrease in the amount of granulocyte colony-stimulating factor (G-CSF; also known as CSF3) and CXCL2 in the lung”
• A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell–mediated tissue damage (2007, background): “IL-17 was also shown to be protective in host defense against Klebesiella pneumoniae”
• Surface phenotype and antigenic specificity of human interleukin 17–producing T helper memory cells (2007, background): “Reports of infectious mouse models have suggested that T H -17 cells developed to mediate protection against extracellular bacteria and fung”
• Innate Lymphoid Cells: a new paradigm in immunology (2015, background): “On the other hand, IL-5 induces the recruitment of eosinophils, and IL-13 stimulates the production ofmucus by goblet cells [the secretion of which can also be induced by IFN-g (60)] (61), whereas IL-17 and IL-22 induce the production of antimicrobial peptides by epithelial cells (62) and the recrui”
• Interleukin-17 family and IL-17 receptors. (2003, background): “pneumoniae challenge, IL-17R KO ↑ Mortality in challenged IL-17R KO mice ↓ MIP-1 -1 ,-2, G-CSF, SCF in challenged KO mice [95]”
• IL-17 family cytokines and the expanding diversity of effector T cell lineages. (2007, background): “Mice with targeted deletion of Il17ra have profound defects in host protection (50), consistent with a critical role for IL-17A and IL-17F in host defense.”
• IL-17-Mediated Regulation of Innate and Acquired Immune Response against Pulmonary Mycobacterium bovis Bacille Calmette-Guérin Infection1 (2007, background): “IL-17 has been reported to be an important mediator of neutrophil migration and host defense against pneumonia by Klebsiella pneumoniae (19, 53).”