Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection

Amanda Stanley, Fabien de Labastida Rivera, Ashraful Haque, Meru Sheel, Yonghong Zhou, Fiona Amante, Patrick Bunn, Louise Randall, Klau Pfeffer, Stefanie Scheu, Michael Hickey, Bernadette Saunders, Carl Ware, Geoffrey Hill, Koji Tamada, Paul Kaye, Christian Engwerda

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Abstract

LIGHT (TNFSF14) is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTI?R). We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL) caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNI?- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTI?R interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4(+) T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage.
Original languageEnglish
Pages (from-to)e1002279 - e1002279
Number of pages15
JournalPLoS Pathogens
Volume7
Issue number10
DOIs
Publication statusPublished - 2011

Cite this

Stanley, A., de Labastida Rivera, F., Haque, A., Sheel, M., Zhou, Y., Amante, F., ... Engwerda, C. (2011). Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection. PLoS Pathogens, 7(10), e1002279 - e1002279. https://doi.org/10.1371/journal.ppat.1002279
Stanley, Amanda ; de Labastida Rivera, Fabien ; Haque, Ashraful ; Sheel, Meru ; Zhou, Yonghong ; Amante, Fiona ; Bunn, Patrick ; Randall, Louise ; Pfeffer, Klau ; Scheu, Stefanie ; Hickey, Michael ; Saunders, Bernadette ; Ware, Carl ; Hill, Geoffrey ; Tamada, Koji ; Kaye, Paul ; Engwerda, Christian. / Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection. In: PLoS Pathogens. 2011 ; Vol. 7, No. 10. pp. e1002279 - e1002279.
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abstract = "LIGHT (TNFSF14) is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTI?R). We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL) caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNI?- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTI?R interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4(+) T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage.",
author = "Amanda Stanley and {de Labastida Rivera}, Fabien and Ashraful Haque and Meru Sheel and Yonghong Zhou and Fiona Amante and Patrick Bunn and Louise Randall and Klau Pfeffer and Stefanie Scheu and Michael Hickey and Bernadette Saunders and Carl Ware and Geoffrey Hill and Koji Tamada and Paul Kaye and Christian Engwerda",
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Stanley, A, de Labastida Rivera, F, Haque, A, Sheel, M, Zhou, Y, Amante, F, Bunn, P, Randall, L, Pfeffer, K, Scheu, S, Hickey, M, Saunders, B, Ware, C, Hill, G, Tamada, K, Kaye, P & Engwerda, C 2011, 'Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection', PLoS Pathogens, vol. 7, no. 10, pp. e1002279 - e1002279. https://doi.org/10.1371/journal.ppat.1002279

Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection. / Stanley, Amanda; de Labastida Rivera, Fabien; Haque, Ashraful; Sheel, Meru; Zhou, Yonghong; Amante, Fiona; Bunn, Patrick; Randall, Louise; Pfeffer, Klau; Scheu, Stefanie; Hickey, Michael; Saunders, Bernadette; Ware, Carl; Hill, Geoffrey; Tamada, Koji; Kaye, Paul; Engwerda, Christian.

In: PLoS Pathogens, Vol. 7, No. 10, 2011, p. e1002279 - e1002279.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Critical roles for LIGHT and its receptors in generating T cell-mediated immunity during Leishmania donovani infection

AU - Stanley, Amanda

AU - de Labastida Rivera, Fabien

AU - Haque, Ashraful

AU - Sheel, Meru

AU - Zhou, Yonghong

AU - Amante, Fiona

AU - Bunn, Patrick

AU - Randall, Louise

AU - Pfeffer, Klau

AU - Scheu, Stefanie

AU - Hickey, Michael

AU - Saunders, Bernadette

AU - Ware, Carl

AU - Hill, Geoffrey

AU - Tamada, Koji

AU - Kaye, Paul

AU - Engwerda, Christian

PY - 2011

Y1 - 2011

N2 - LIGHT (TNFSF14) is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTI?R). We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL) caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNI?- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTI?R interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4(+) T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage.

AB - LIGHT (TNFSF14) is a member of the TNF superfamily involved in inflammation and defence against infection. LIGHT signals via two cell-bound receptors; herpes virus entry mediator (HVEM) and lymphotoxin-beta receptor (LTI?R). We found that LIGHT is critical for control of hepatic parasite growth in mice with visceral leishmaniasis (VL) caused by infection with the protozoan parasite Leishmania donovani. LIGHT-HVEM signalling is essential for early dendritic cell IL-12/IL-23p40 production, and the generation of IFNI?- and TNF-producing T cells that control hepatic infection. However, we also discovered that LIGHT-LTI?R interactions suppress anti-parasitic immunity in the liver in the first 7 days of infection by mechanisms that restrict both CD4(+) T cell function and TNF-dependent microbicidal mechanisms. Thus, we have identified distinct roles for LIGHT in infection, and show that manipulation of interactions between LIGHT and its receptors may be used for therapeutic advantage.

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U2 - 10.1371/journal.ppat.1002279

DO - 10.1371/journal.ppat.1002279

M3 - Article

VL - 7

SP - e1002279 - e1002279

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 10

ER -