Spatiotemporal requirements for IRF7 in mediating type I IFN-dependent susceptibility to blood-stage Plasmodium infection

Chelsea L Edwards, Shannon E Best, Sin Yee Gun, Carla Claser, Kylie R James, Marcela Montes de Oca, Ismail Sebina, Fabian Rivera de Labastida Rivera, Fiona H Amante, Paul John Hertzog, Christian R Engwerda, Laurent Renia, Ashraful K M Nazmul Haque

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

Type I IFN signaling suppresses splenic T helper 1 (Th1) responses during blood-stage Plasmodium berghei ANKA (PbA) infection in mice, and is crucial for mediating tissue accumulation of parasites and fatal cerebral symptoms via mechanisms that remain to be fully characterized. Interferon regulatory factor 7 (IRF7) is considered to be a master regulator of type I IFN responses. Here, we assessed IRF7 for its roles during lethal PbA infection and nonlethal Plasmodium chabaudi chabaudi AS (PcAS) infection as two distinct models of blood-stage malaria. We found that IRF7 was not essential for tissue accumulation of parasites, cerebral symptoms, or brain pathology. Using timed administration of anti-IFNAR1 mAb, we show that late IFNAR1 signaling promotes fatal disease via IRF7-independent mechanisms. Despite this, IRF7 significantly impaired early splenic Th1 responses and limited control of parasitemia during PbA infection. Finally, IRF7 also suppressed antiparasitic immunity and Th1 responses during nonlethal PcAS infection. Together, our data support a model in which IRF7 suppresses antiparasitic immunity in the spleen, while IFNAR1-mediated, but IRF7-independent, signaling contributes to pathology in the brain during experimental blood-stage malaria.
Original languageEnglish
Pages (from-to)130 - 141
Number of pages12
JournalEuropean Journal of Immunology
Volume45
Issue number1
DOIs
Publication statusPublished - 2015

Cite this

Edwards, C. L., Best, S. E., Gun, S. Y., Claser, C., James, K. R., Montes de Oca, M., ... Haque, A. K. M. N. (2015). Spatiotemporal requirements for IRF7 in mediating type I IFN-dependent susceptibility to blood-stage Plasmodium infection. European Journal of Immunology, 45(1), 130 - 141. https://doi.org/10.1002/eji.201444824
Edwards, Chelsea L ; Best, Shannon E ; Gun, Sin Yee ; Claser, Carla ; James, Kylie R ; Montes de Oca, Marcela ; Sebina, Ismail ; de Labastida Rivera, Fabian Rivera ; Amante, Fiona H ; Hertzog, Paul John ; Engwerda, Christian R ; Renia, Laurent ; Haque, Ashraful K M Nazmul. / Spatiotemporal requirements for IRF7 in mediating type I IFN-dependent susceptibility to blood-stage Plasmodium infection. In: European Journal of Immunology. 2015 ; Vol. 45, No. 1. pp. 130 - 141.
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title = "Spatiotemporal requirements for IRF7 in mediating type I IFN-dependent susceptibility to blood-stage Plasmodium infection",
abstract = "Type I IFN signaling suppresses splenic T helper 1 (Th1) responses during blood-stage Plasmodium berghei ANKA (PbA) infection in mice, and is crucial for mediating tissue accumulation of parasites and fatal cerebral symptoms via mechanisms that remain to be fully characterized. Interferon regulatory factor 7 (IRF7) is considered to be a master regulator of type I IFN responses. Here, we assessed IRF7 for its roles during lethal PbA infection and nonlethal Plasmodium chabaudi chabaudi AS (PcAS) infection as two distinct models of blood-stage malaria. We found that IRF7 was not essential for tissue accumulation of parasites, cerebral symptoms, or brain pathology. Using timed administration of anti-IFNAR1 mAb, we show that late IFNAR1 signaling promotes fatal disease via IRF7-independent mechanisms. Despite this, IRF7 significantly impaired early splenic Th1 responses and limited control of parasitemia during PbA infection. Finally, IRF7 also suppressed antiparasitic immunity and Th1 responses during nonlethal PcAS infection. Together, our data support a model in which IRF7 suppresses antiparasitic immunity in the spleen, while IFNAR1-mediated, but IRF7-independent, signaling contributes to pathology in the brain during experimental blood-stage malaria.",
author = "Edwards, {Chelsea L} and Best, {Shannon E} and Gun, {Sin Yee} and Carla Claser and James, {Kylie R} and {Montes de Oca}, Marcela and Ismail Sebina and {de Labastida Rivera}, {Fabian Rivera} and Amante, {Fiona H} and Hertzog, {Paul John} and Engwerda, {Christian R} and Laurent Renia and Haque, {Ashraful K M Nazmul}",
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Edwards, CL, Best, SE, Gun, SY, Claser, C, James, KR, Montes de Oca, M, Sebina, I, de Labastida Rivera, FR, Amante, FH, Hertzog, PJ, Engwerda, CR, Renia, L & Haque, AKMN 2015, 'Spatiotemporal requirements for IRF7 in mediating type I IFN-dependent susceptibility to blood-stage Plasmodium infection', European Journal of Immunology, vol. 45, no. 1, pp. 130 - 141. https://doi.org/10.1002/eji.201444824

Spatiotemporal requirements for IRF7 in mediating type I IFN-dependent susceptibility to blood-stage Plasmodium infection. / Edwards, Chelsea L; Best, Shannon E; Gun, Sin Yee; Claser, Carla; James, Kylie R; Montes de Oca, Marcela; Sebina, Ismail; de Labastida Rivera, Fabian Rivera; Amante, Fiona H; Hertzog, Paul John; Engwerda, Christian R; Renia, Laurent; Haque, Ashraful K M Nazmul.

In: European Journal of Immunology, Vol. 45, No. 1, 2015, p. 130 - 141.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Spatiotemporal requirements for IRF7 in mediating type I IFN-dependent susceptibility to blood-stage Plasmodium infection

AU - Edwards, Chelsea L

AU - Best, Shannon E

AU - Gun, Sin Yee

AU - Claser, Carla

AU - James, Kylie R

AU - Montes de Oca, Marcela

AU - Sebina, Ismail

AU - de Labastida Rivera, Fabian Rivera

AU - Amante, Fiona H

AU - Hertzog, Paul John

AU - Engwerda, Christian R

AU - Renia, Laurent

AU - Haque, Ashraful K M Nazmul

PY - 2015

Y1 - 2015

N2 - Type I IFN signaling suppresses splenic T helper 1 (Th1) responses during blood-stage Plasmodium berghei ANKA (PbA) infection in mice, and is crucial for mediating tissue accumulation of parasites and fatal cerebral symptoms via mechanisms that remain to be fully characterized. Interferon regulatory factor 7 (IRF7) is considered to be a master regulator of type I IFN responses. Here, we assessed IRF7 for its roles during lethal PbA infection and nonlethal Plasmodium chabaudi chabaudi AS (PcAS) infection as two distinct models of blood-stage malaria. We found that IRF7 was not essential for tissue accumulation of parasites, cerebral symptoms, or brain pathology. Using timed administration of anti-IFNAR1 mAb, we show that late IFNAR1 signaling promotes fatal disease via IRF7-independent mechanisms. Despite this, IRF7 significantly impaired early splenic Th1 responses and limited control of parasitemia during PbA infection. Finally, IRF7 also suppressed antiparasitic immunity and Th1 responses during nonlethal PcAS infection. Together, our data support a model in which IRF7 suppresses antiparasitic immunity in the spleen, while IFNAR1-mediated, but IRF7-independent, signaling contributes to pathology in the brain during experimental blood-stage malaria.

AB - Type I IFN signaling suppresses splenic T helper 1 (Th1) responses during blood-stage Plasmodium berghei ANKA (PbA) infection in mice, and is crucial for mediating tissue accumulation of parasites and fatal cerebral symptoms via mechanisms that remain to be fully characterized. Interferon regulatory factor 7 (IRF7) is considered to be a master regulator of type I IFN responses. Here, we assessed IRF7 for its roles during lethal PbA infection and nonlethal Plasmodium chabaudi chabaudi AS (PcAS) infection as two distinct models of blood-stage malaria. We found that IRF7 was not essential for tissue accumulation of parasites, cerebral symptoms, or brain pathology. Using timed administration of anti-IFNAR1 mAb, we show that late IFNAR1 signaling promotes fatal disease via IRF7-independent mechanisms. Despite this, IRF7 significantly impaired early splenic Th1 responses and limited control of parasitemia during PbA infection. Finally, IRF7 also suppressed antiparasitic immunity and Th1 responses during nonlethal PcAS infection. Together, our data support a model in which IRF7 suppresses antiparasitic immunity in the spleen, while IFNAR1-mediated, but IRF7-independent, signaling contributes to pathology in the brain during experimental blood-stage malaria.

UR - http://onlinelibrary.wiley.com/doi/10.1002/eji.201444824/pdf

U2 - 10.1002/eji.201444824

DO - 10.1002/eji.201444824

M3 - Article

VL - 45

SP - 130

EP - 141

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 1

ER -