Eosinophils preserve parasitic nematode larvae by regulating local immunity

Nebiat G. Gebreselassie, Andrew R. Moorhead, Valeria Fabre, Lucille F. Gagliardo, Nancy A Lee, James J. Lee, Judith A. Appleton

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Eosinophils play important roles in regulation of cellular responses under conditions of homeostasis or infection. Intestinal infection with the parasitic nematode, Trichinella spiralis, induces a pronounced eosinophilia that coincides with establishment of larval stages in skeletal muscle.We have shown previously that in mouse strains in which the eosinophil lineage is ablated, large numbers of T. spiralis larvae are killed by NO, implicating the eosinophil as an immune regulator. In this report, we show that parasite death in eosinophil-ablated mice correlates with reduced recruitment of IL-4 + T cells and enhanced recruitment of inducible NO synthase (iNOS)-producing neutrophils to infected muscle, as well as increased iNOS in local F4/80 +CD11b +Ly6C + macrophages. Actively growing T. spiralis larvae were susceptible to killing by NO in vitro, whereas mature larvae were highly resistant. Growth of larvae was impaired in eosinophil-ablated mice, potentially extending the period of susceptibility to the effects of NO and enhancing parasite clearance. Transfer of eosinophils into eosinophil-ablated ΔdblGATA mice restored larval growth and survival. Regulation of immunity was not dependent upon eosinophil peroxidase or major basic protein 1 and did not correlate with activity of the IDO pathway. Our results suggest that eosinophils support parasite growth and survival by promoting accumulation of Th2 cells and preventing induction of iNOS in macrophages and neutrophils. These findings begin to define the cellular interactions that occur at an extraintestinal site of nematode infection in which the eosinophil functions as a pivotal regulator of immunity.

Original languageEnglish (US)
Pages (from-to)417-425
Number of pages9
JournalJournal of Immunology
Volume188
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

Eosinophils
Larva
Immunity
Trichinella spiralis
Nitric Oxide Synthase
Parasites
Neutrophils
Growth
Eosinophil Peroxidase
Macrophages
Nematode Infections
Th2 Cells
Parasitic Diseases
Eosinophilia
Interleukin-4
Skeletal Muscle
Homeostasis
T-Lymphocytes
Muscles
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Gebreselassie, N. G., Moorhead, A. R., Fabre, V., Gagliardo, L. F., Lee, N. A., Lee, J. J., & Appleton, J. A. (2012). Eosinophils preserve parasitic nematode larvae by regulating local immunity. Journal of Immunology, 188(1), 417-425. https://doi.org/10.4049/jimmunol.1101980

Eosinophils preserve parasitic nematode larvae by regulating local immunity. / Gebreselassie, Nebiat G.; Moorhead, Andrew R.; Fabre, Valeria; Gagliardo, Lucille F.; Lee, Nancy A; Lee, James J.; Appleton, Judith A.

In: Journal of Immunology, Vol. 188, No. 1, 01.01.2012, p. 417-425.

Research output: Contribution to journalArticle

Gebreselassie, NG, Moorhead, AR, Fabre, V, Gagliardo, LF, Lee, NA, Lee, JJ & Appleton, JA 2012, 'Eosinophils preserve parasitic nematode larvae by regulating local immunity', Journal of Immunology, vol. 188, no. 1, pp. 417-425. https://doi.org/10.4049/jimmunol.1101980
Gebreselassie NG, Moorhead AR, Fabre V, Gagliardo LF, Lee NA, Lee JJ et al. Eosinophils preserve parasitic nematode larvae by regulating local immunity. Journal of Immunology. 2012 Jan 1;188(1):417-425. https://doi.org/10.4049/jimmunol.1101980
Gebreselassie, Nebiat G. ; Moorhead, Andrew R. ; Fabre, Valeria ; Gagliardo, Lucille F. ; Lee, Nancy A ; Lee, James J. ; Appleton, Judith A. / Eosinophils preserve parasitic nematode larvae by regulating local immunity. In: Journal of Immunology. 2012 ; Vol. 188, No. 1. pp. 417-425.
@article{63f0ed738944426da3efa7d2b3917473,
title = "Eosinophils preserve parasitic nematode larvae by regulating local immunity",
abstract = "Eosinophils play important roles in regulation of cellular responses under conditions of homeostasis or infection. Intestinal infection with the parasitic nematode, Trichinella spiralis, induces a pronounced eosinophilia that coincides with establishment of larval stages in skeletal muscle.We have shown previously that in mouse strains in which the eosinophil lineage is ablated, large numbers of T. spiralis larvae are killed by NO, implicating the eosinophil as an immune regulator. In this report, we show that parasite death in eosinophil-ablated mice correlates with reduced recruitment of IL-4 + T cells and enhanced recruitment of inducible NO synthase (iNOS)-producing neutrophils to infected muscle, as well as increased iNOS in local F4/80 +CD11b +Ly6C + macrophages. Actively growing T. spiralis larvae were susceptible to killing by NO in vitro, whereas mature larvae were highly resistant. Growth of larvae was impaired in eosinophil-ablated mice, potentially extending the period of susceptibility to the effects of NO and enhancing parasite clearance. Transfer of eosinophils into eosinophil-ablated ΔdblGATA mice restored larval growth and survival. Regulation of immunity was not dependent upon eosinophil peroxidase or major basic protein 1 and did not correlate with activity of the IDO pathway. Our results suggest that eosinophils support parasite growth and survival by promoting accumulation of Th2 cells and preventing induction of iNOS in macrophages and neutrophils. These findings begin to define the cellular interactions that occur at an extraintestinal site of nematode infection in which the eosinophil functions as a pivotal regulator of immunity.",
author = "Gebreselassie, {Nebiat G.} and Moorhead, {Andrew R.} and Valeria Fabre and Gagliardo, {Lucille F.} and Lee, {Nancy A} and Lee, {James J.} and Appleton, {Judith A.}",
year = "2012",
month = "1",
day = "1",
doi = "10.4049/jimmunol.1101980",
language = "English (US)",
volume = "188",
pages = "417--425",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

TY - JOUR

T1 - Eosinophils preserve parasitic nematode larvae by regulating local immunity

AU - Gebreselassie, Nebiat G.

AU - Moorhead, Andrew R.

AU - Fabre, Valeria

AU - Gagliardo, Lucille F.

AU - Lee, Nancy A

AU - Lee, James J.

AU - Appleton, Judith A.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Eosinophils play important roles in regulation of cellular responses under conditions of homeostasis or infection. Intestinal infection with the parasitic nematode, Trichinella spiralis, induces a pronounced eosinophilia that coincides with establishment of larval stages in skeletal muscle.We have shown previously that in mouse strains in which the eosinophil lineage is ablated, large numbers of T. spiralis larvae are killed by NO, implicating the eosinophil as an immune regulator. In this report, we show that parasite death in eosinophil-ablated mice correlates with reduced recruitment of IL-4 + T cells and enhanced recruitment of inducible NO synthase (iNOS)-producing neutrophils to infected muscle, as well as increased iNOS in local F4/80 +CD11b +Ly6C + macrophages. Actively growing T. spiralis larvae were susceptible to killing by NO in vitro, whereas mature larvae were highly resistant. Growth of larvae was impaired in eosinophil-ablated mice, potentially extending the period of susceptibility to the effects of NO and enhancing parasite clearance. Transfer of eosinophils into eosinophil-ablated ΔdblGATA mice restored larval growth and survival. Regulation of immunity was not dependent upon eosinophil peroxidase or major basic protein 1 and did not correlate with activity of the IDO pathway. Our results suggest that eosinophils support parasite growth and survival by promoting accumulation of Th2 cells and preventing induction of iNOS in macrophages and neutrophils. These findings begin to define the cellular interactions that occur at an extraintestinal site of nematode infection in which the eosinophil functions as a pivotal regulator of immunity.

AB - Eosinophils play important roles in regulation of cellular responses under conditions of homeostasis or infection. Intestinal infection with the parasitic nematode, Trichinella spiralis, induces a pronounced eosinophilia that coincides with establishment of larval stages in skeletal muscle.We have shown previously that in mouse strains in which the eosinophil lineage is ablated, large numbers of T. spiralis larvae are killed by NO, implicating the eosinophil as an immune regulator. In this report, we show that parasite death in eosinophil-ablated mice correlates with reduced recruitment of IL-4 + T cells and enhanced recruitment of inducible NO synthase (iNOS)-producing neutrophils to infected muscle, as well as increased iNOS in local F4/80 +CD11b +Ly6C + macrophages. Actively growing T. spiralis larvae were susceptible to killing by NO in vitro, whereas mature larvae were highly resistant. Growth of larvae was impaired in eosinophil-ablated mice, potentially extending the period of susceptibility to the effects of NO and enhancing parasite clearance. Transfer of eosinophils into eosinophil-ablated ΔdblGATA mice restored larval growth and survival. Regulation of immunity was not dependent upon eosinophil peroxidase or major basic protein 1 and did not correlate with activity of the IDO pathway. Our results suggest that eosinophils support parasite growth and survival by promoting accumulation of Th2 cells and preventing induction of iNOS in macrophages and neutrophils. These findings begin to define the cellular interactions that occur at an extraintestinal site of nematode infection in which the eosinophil functions as a pivotal regulator of immunity.

UR - http://www.scopus.com/inward/record.url?scp=84855384507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855384507&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1101980

DO - 10.4049/jimmunol.1101980

M3 - Article

C2 - 22131328

AN - SCOPUS:84855384507

VL - 188

SP - 417

EP - 425

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -