Neutrophil Migration into the Infected Uroepithelium Is Regulated by the Crosstalk between Resident and Helper Macrophages

Kristina Zec; Julia Volke; Nirojah Vijitha; Stephanie Thiebes; Matthias Gunzer; Christian Kurts; Daniel Robert Engel

doi:10.3390/pathogens5010015

Neutrophil Migration into the Infected Uroepithelium Is Regulated by the Crosstalk between Resident and Helper Macrophages

Pathogens. 2016 Feb 4;5(1):15. doi: 10.3390/pathogens5010015.

Authors

Kristina Zec¹, Julia Volke², Nirojah Vijitha³, Stephanie Thiebes⁴, Matthias Gunzer⁵, Christian Kurts⁶, Daniel Robert Engel⁷

Affiliations

¹ Institute of Experimental Immunology and Imaging, Department Immunodynamics, University Hospital Essen, University Duisburg-Essen, Essen 45141, Germany. [email protected].
² Institute of Experimental Immunology and Imaging, Department Immunodynamics, University Hospital Essen, University Duisburg-Essen, Essen 45141, Germany. [email protected].
³ Institute of Experimental Immunology and Imaging, Department Immunodynamics, University Hospital Essen, University Duisburg-Essen, Essen 45141, Germany. [email protected].
⁴ Institute of Experimental Immunology and Imaging, Department Immunodynamics, University Hospital Essen, University Duisburg-Essen, Essen 45141, Germany. [email protected].
⁵ Institute of Experimental Immunology and Imaging, Department Immunodynamics, University Hospital Essen, University Duisburg-Essen, Essen 45141, Germany. [email protected].
⁶ Institute of Experimental Immunology, University Hospital Bonn, Bonn 53127, Germany. [email protected].
⁷ Institute of Experimental Immunology and Imaging, Department Immunodynamics, University Hospital Essen, University Duisburg-Essen, Essen 45141, Germany. [email protected].

Abstract

The antibacterial defense against infections depends on the cooperation between distinct phagocytes of the innate immune system, namely macrophages and neutrophils. However, the mechanisms driving this cooperation are incompletely understood. In this study we describe the crosstalk between Ly6C⁺ and Ly6C(-) macrophage-subtypes and neutrophils in the context of urinary tract infection (UTI) with uropathogenic E. coli (UPEC). Ly6C(-) macrophages acted as tissue resident sentinels and attracted circulating phagocytes by chemokines. Ly6C⁺ macrophages produced tumor necrosis factor (TNF) that licensed Ly6C(-) macrophages to release preformed CXCL2, which in turn caused matrix metalloproteinases (MMP-9) secretion by neutrophils to enable transepithelial migration.

Keywords: Ly6C+ and Ly6C− macrophages; crosstalk; neutrophils; transepithelial migration; uropathogenic E. coli (UPEC).