PAD4 controls chemoattractant production and neutrophil trafficking in malaria

Drinalda Cela; Sebastian Lorenz Knackstedt; Sarah J Groves; Christopher M Rice; Jamie Tae Wook Kwon; Benjamin Mordmüller; Borko Amulic

doi:10.1002/JLB.4AB1120-780R

PAD4 controls chemoattractant production and neutrophil trafficking in malaria

Drinalda Cela, Sebastian Lorenz Knackstedt, Sarah J Groves, Christopher M Rice, Jamie Tae Wook Kwon, Benjamin Mordmüller, Borko Amulic^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

Peptidylarginine deiminase 4 (PAD4) is a key regulator of inflammation but its function in infections remains incompletely understood. We investigate PAD4 in the context of malaria and demonstrate a role in regulation of immune cell trafficking and chemokine production. PAD4 regulates liver immunopathology by promoting neutrophil trafficking in a Plasmodium chabaudi mouse malaria model. In human macrophages, PAD4 regulates expression of CXCL chemokines in response to stimulation with TLR ligands and P. falciparum. Using patient samples, we show that CXCL1 may be a biomarker for severe malaria. PAD4 inhibition promotes disease tolerance and may represent a therapeutic avenue in malaria.

Original language	English
Pages (from-to)	1235–1242
Number of pages	8
Journal	Journal of Leukocyte Biology
Volume	111
Issue number	6
Early online date	10 Nov 2021
DOIs	https://doi.org/10.1002/JLB.4AB1120-780R
Publication status	Published - 1 Jun 2022

Keywords

chemokine
malaria
neutrophil
PAD4

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title = "PAD4 controls chemoattractant production and neutrophil trafficking in malaria",

abstract = "Peptidylarginine deiminase 4 (PAD4) is a key regulator of inflammation but its function in infections remains incompletely understood. We investigate PAD4 in the context of malaria and demonstrate a role in regulation of immune cell trafficking and chemokine production. PAD4 regulates liver immunopathology by promoting neutrophil trafficking in a Plasmodium chabaudi mouse malaria model. In human macrophages, PAD4 regulates expression of CXCL chemokines in response to stimulation with TLR ligands and P. falciparum. Using patient samples, we show that CXCL1 may be a biomarker for severe malaria. PAD4 inhibition promotes disease tolerance and may represent a therapeutic avenue in malaria.",

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author = "Drinalda Cela and Knackstedt, {Sebastian Lorenz} and Groves, {Sarah J} and Rice, {Christopher M} and Kwon, {Jamie Tae Wook} and Benjamin Mordm{\"u}ller and Borko Amulic",

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doi = "10.1002/JLB.4AB1120-780R",

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TY - JOUR

T1 - PAD4 controls chemoattractant production and neutrophil trafficking in malaria

AU - Cela, Drinalda

AU - Knackstedt, Sebastian Lorenz

AU - Groves, Sarah J

AU - Rice, Christopher M

AU - Kwon, Jamie Tae Wook

AU - Mordmüller, Benjamin

AU - Amulic, Borko

PY - 2022/6/1

Y1 - 2022/6/1

N2 - Peptidylarginine deiminase 4 (PAD4) is a key regulator of inflammation but its function in infections remains incompletely understood. We investigate PAD4 in the context of malaria and demonstrate a role in regulation of immune cell trafficking and chemokine production. PAD4 regulates liver immunopathology by promoting neutrophil trafficking in a Plasmodium chabaudi mouse malaria model. In human macrophages, PAD4 regulates expression of CXCL chemokines in response to stimulation with TLR ligands and P. falciparum. Using patient samples, we show that CXCL1 may be a biomarker for severe malaria. PAD4 inhibition promotes disease tolerance and may represent a therapeutic avenue in malaria.

AB - Peptidylarginine deiminase 4 (PAD4) is a key regulator of inflammation but its function in infections remains incompletely understood. We investigate PAD4 in the context of malaria and demonstrate a role in regulation of immune cell trafficking and chemokine production. PAD4 regulates liver immunopathology by promoting neutrophil trafficking in a Plasmodium chabaudi mouse malaria model. In human macrophages, PAD4 regulates expression of CXCL chemokines in response to stimulation with TLR ligands and P. falciparum. Using patient samples, we show that CXCL1 may be a biomarker for severe malaria. PAD4 inhibition promotes disease tolerance and may represent a therapeutic avenue in malaria.

KW - chemokine

KW - malaria

KW - neutrophil

KW - PAD4

U2 - 10.1002/JLB.4AB1120-780R

DO - 10.1002/JLB.4AB1120-780R

M3 - Article (Academic Journal)

C2 - 34755385

SN - 0741-5400

VL - 111

SP - 1235

EP - 1242

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

IS - 6

ER -

PAD4 controls chemoattractant production and neutrophil trafficking in malaria

Abstract

Keywords

UN SDGs

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