title: Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury.
abstract: It has become increasingly clear that the functions of eosinophils extend beyond host defense and allergy to metabolism and tissue regeneration. These influences have strong potential to be relevant in worm infections in which eosinophils are prominent and parasites rely on the host for nutrients to support growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle. Our results indicate that IL-4 and eosinophils are necessary for normal larval growth and that eosinophils from IL-4 competent mice are sufficient to support growth. The eosinophil-mediated effect operates in the absence of adaptive immunity. Following invasion by newborn larvae, host gene expression in skeletal muscle was compatible with a regenerative response and a shift in the source of energy in infected tissue. The presence of eosinophils suppressed local inflammation while also influencing nutrient homeostasis in muscle. Redistribution of glucose transporter 4 (GLUT4) and phosphorylation of Akt were observed in nurse cells, consistent with enhancement of glucose uptake and glycogen storage by larvae that is known to occur. The data are consistent with a mechanism in which eosinophils promote larval growth by an IL-4 dependent mechanism that limits local interferon-driven responses that otherwise alter nutrient metabolism in infected muscle. Our findings document a novel interaction between parasite and host in which worms have evolved a strategy to co-opt an innate host cell response in a way that facilitates their growth.
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Beiting
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Nebiat G
authors.initials: NG
authors.lastname: Gebreselassie
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Lucille F
authors.initials: LF
authors.lastname: Gagliardo
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Maura C
authors.initials: MC
authors.lastname: Ruyechan
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Hematology/Oncology, Mayo Clinic Arizona, Scottsdale, Arizona, United States of America.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Pulmonary Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Appleton
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology*; D006790:Host-Parasite Interactions / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017160:Trichinella spiralis / Q000276:immunology; D014235:Trichinellosis / Q000276:immunology*
chemical_list: D015847:Interleukin-4