Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage.

Tara Sutherland; Nicola Logan; Dominik Ruckerl; Alison A Humbles; Stuart Allan; Venizelos Papayannopoulos; Brigitta Stockinger; Rick M Maizels; Judith Allen

doi:10.1038/ni.3023

Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage.

Tara Sutherland, Nicola Logan, Dominik Ruckerl, Alison A Humbles, Stuart Allan, Venizelos Papayannopoulos, Brigitta Stockinger, Rick M Maizels, Judith Allen

Medical Sciences

Research output: Contribution to journal › Article › peer-review

160 Citations (Scopus)

Abstract

Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family.

Original language	English
Pages (from-to)	1116-1125
Number of pages	10
Journal	Nature Immunology
Volume	15
Issue number	12
DOIs	https://doi.org/10.1038/ni.3023
Publication status	Published - 19 Oct 2014

Bibliographical note

Acknowledgements
We thank S. Duncan and Y. Harcus for technical assistance and R. Zamoyska for discussions. Supported by the Medical Research Council United Kingdom (MRC-UK MR/J001929/1, MR/K01207X/1 and U117512792 to B.S., and MC_UP_1202/13 for V.P.) and Asthma UK (06/057 & 10/040), with support from the Wellcome Trust funded Centre for Immunity, Infection and Evolution. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Access to Document

10.1038/ni.3023

Cite this

@article{7fde5d27c3da49b8bd235d0aa1829b3b,

title = "Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage.",

abstract = "Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family.",

author = "Tara Sutherland and Nicola Logan and Dominik Ruckerl and Humbles, {Alison A} and Stuart Allan and Venizelos Papayannopoulos and Brigitta Stockinger and Maizels, {Rick M} and Judith Allen",

note = "Acknowledgements We thank S. Duncan and Y. Harcus for technical assistance and R. Zamoyska for discussions. Supported by the Medical Research Council United Kingdom (MRC-UK MR/J001929/1, MR/K01207X/1 and U117512792 to B.S., and MC_UP_1202/13 for V.P.) and Asthma UK (06/057 & 10/040), with support from the Wellcome Trust funded Centre for Immunity, Infection and Evolution. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript",

year = "2014",

month = oct,

day = "19",

doi = "10.1038/ni.3023",

language = "English",

volume = "15",

pages = "1116--1125",

journal = "Nature Immunology",

issn = "1529-2916",

publisher = "Nature Publishing Group",

number = "12",

}

TY - JOUR

T1 - Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage.

AU - Sutherland, Tara

AU - Logan, Nicola

AU - Ruckerl, Dominik

AU - Humbles, Alison A

AU - Allan, Stuart

AU - Papayannopoulos, Venizelos

AU - Stockinger, Brigitta

AU - Maizels, Rick M

AU - Allen, Judith

N1 - Acknowledgements We thank S. Duncan and Y. Harcus for technical assistance and R. Zamoyska for discussions. Supported by the Medical Research Council United Kingdom (MRC-UK MR/J001929/1, MR/K01207X/1 and U117512792 to B.S., and MC_UP_1202/13 for V.P.) and Asthma UK (06/057 & 10/040), with support from the Wellcome Trust funded Centre for Immunity, Infection and Evolution. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

PY - 2014/10/19

Y1 - 2014/10/19

N2 - Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family.

AB - Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family.

U2 - 10.1038/ni.3023

DO - 10.1038/ni.3023

M3 - Article

SN - 1529-2916

VL - 15

SP - 1116

EP - 1125

JO - Nature Immunology

JF - Nature Immunology

IS - 12

ER -

Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage.

Abstract

Bibliographical note

Access to Document

Fingerprint

Cite this