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Immunity. 2016 Jul 19;45(1):172-84. doi: 10.1016/j.immuni.2016.06.025.

Type 2 Interleukin-4 Receptor Signaling in Neutrophils Antagonizes Their Expansion and Migration during Infection and Inflammation.

Author information

1
Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
2
Department of Infectious Diseases, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland.
3
Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
4
Immunopathogenesis Section, Program in Barrier Immunity and Repair, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, NIH, Bethesda, MD 20892-0425, USA.
5
Department of Immunology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland. Electronic address: onur.boyman@uzh.ch.

Abstract

Neutrophils are the first immune cells recruited to sites of inflammation and infection. However, patients with allergic disorders such as atopic dermatitis show a paucity of skin neutrophils and are prone to bacterial skin infections, suggesting that allergic inflammation curtails neutrophil responses. Here we have shown that the type 2 cell signature cytokine interleukin-4 (IL-4) hampers neutrophil expansion and migration by antagonizing granulocyte colony-stimulating factor (G-CSF) and chemokine receptor-mediated signals. Cutaneous bacterial infection in mice was exacerbated by IL-4 signaling and improved with IL-4 inhibition, each outcome inversely correlating with neutrophil migration to skin. Likewise, systemic bacterial infection was worsened by heightened IL-4 activity, with IL-4 restricting G-CSF-induced neutrophil expansion and migration to tissues by affecting CXCR2-CXCR4 chemokine signaling in neutrophils. These effects were dependent on IL-4 acting through type 2 IL-4 receptors on neutrophils. Thus, targeting IL-4 might be beneficial in neutropenic conditions with increased susceptibility to bacterial infections.

PMID:
27438770
DOI:
10.1016/j.immuni.2016.06.025
[Indexed for MEDLINE]
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