Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia

Turner, Joseph ORCID: https://orcid.org/0000-0002-2185-5476, Pionnier, Nicolas ORCID: https://orcid.org/0000-0002-2379-4945, Furlong-Silva, Julio, Sjoberg, Hanna, Cross, Stephen, Halliday, Alice, Guimaraes, Ana, Cook, Darren, Steven, Andrew, Van Rooijen, Nico, Allen, Judith, Jenkins, Stephen and Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 (2018) 'Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia'. PLoS Pathogens, Vol 14, Issue 3, e1006949.

Preview

Text Plos_Pathogens_14_3_e1006949_2018.pdf - Published Version Available under License Creative Commons Attribution. Download (5MB) | Preview

Abstract

Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection. Post-infection, peritoneal Mϕ populations proliferated and became alternatively-activated (AAMϕ). Filarial AAMϕ development required adaptive immunity and interleukin-4 receptor-alpha. Depletion of Mϕ prior to infection suppressed eosinophilia and facilitated worm survival. Add back of filarial AAMϕ in Mϕ-depleted mice recapitulated a vigorous eosinophilia. Transfer of filarial AAMϕ into Severe-Combined Immune Deficient mice mediated immunological resistance in an eosinophil-dependent manner. Exogenous IL-4 delivery recapitulated tissue AAMϕ expansions, sustained eosinophilia and mediated immunological resistance in Mϕ-intact SCID mice. Co-culturing Brugia with filarial AAMϕ and/or filarial-recruited eosinophils confirmed eosinophils as the larvicidal cell type. Our data demonstrates that IL-4/IL-4Rα activated AAMϕ orchestrate eosinophil immunity to filarial tissue helminth infection.

Item Type:	Article
Subjects:	QU Biochemistry > QU 4 General works QW Microbiology and Immunology > Reference Works. General Immunology > QW 504 General works QW Microbiology and Immunology > QW 51 Morphology and variability of microorganisms. Microbial genetics. QX Parasitology > Helminths. Annelida > QX 200 Helminths QX Parasitology > Helminths. Annelida > QX 301 Filarioidea QX Parasitology > QX 4 General works WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 200 Leukocytes. Leukocyte disorders (General)
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.ppat.1006949
SWORD Depositor:	JISC Pubrouter
Depositing User:	Stacy Murtagh
Date Deposited:	28 Mar 2018 10:20
Last Modified:	17 Jul 2020 10:59
URI:	https://archive.lstmed.ac.uk/id/eprint/8391

Statistics

View details

Actions (login required)

Edit Item