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

Turner, Joseph, Pionnier, Nicolas, 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 (2018) 'Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia'. PLoS Pathogens, Vol 14, Issue 3, e1006949.

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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 > Parasitology Department
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: 29 Mar 2018 08:15
URI: http://archive.lstmed.ac.uk/id/eprint/8391

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