PortalPublikationenC5a-licensed phagocytes drive sterilizing immunity during sy...

C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection

Standard

C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection. / Desai, Jigar V; Kumar, Dhaneshwar; Freiwald, Tilo; Chauss, Daniel; Johnson, Melissa D; Abers, Michael S; Steinbrink, Julie M; Perfect, John R; Alexander, Barbara; Matzaraki, Vasiliki; Snarr, Brendan D; Zarakas, Marissa A; Oikonomou, Vasileios; Silva, Lakmali M; Shivarathri, Raju; Beltran, Emily; Demontel, Luciana Negro; Wang, Luopin; Lim, Jean K; Launder, Dylan; Conti, Heather R; Swamydas, Muthulekha; McClain, Micah T; Moutsopoulos, Niki M; Kazemian, Majid; Netea, Mihai G; Kumar, Vinod; Köhl, Jörg; Kemper, Claudia; Afzali, Behdad; Lionakis, Michail S.

in: CELL, Jahrgang 186, Nr. 13, 22.06.2023, S. 2802-2822.e22.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Desai, JV, Kumar, D, Freiwald, T, Chauss, D, Johnson, MD, Abers, MS, Steinbrink, JM, Perfect, JR, Alexander, B, Matzaraki, V, Snarr, BD, Zarakas, MA, Oikonomou, V, Silva, LM, Shivarathri, R, Beltran, E, Demontel, LN, Wang, L, Lim, JK, Launder, D, Conti, HR, Swamydas, M, McClain, MT, Moutsopoulos, NM, Kazemian, M, Netea, MG, Kumar, V, Köhl, J, Kemper, C, Afzali, B & Lionakis, MS 2023, 'C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection', CELL, Jg. 186, Nr. 13, S. 2802-2822.e22. https://doi.org/10.1016/j.cell.2023.04.031

APA

Desai, J. V., Kumar, D., Freiwald, T., Chauss, D., Johnson, M. D., Abers, M. S., Steinbrink, J. M., Perfect, J. R., Alexander, B., Matzaraki, V., Snarr, B. D., Zarakas, M. A., Oikonomou, V., Silva, L. M., Shivarathri, R., Beltran, E., Demontel, L. N., Wang, L., Lim, J. K., ... Lionakis, M. S. (2023). C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection. CELL, 186(13), 2802-2822.e22. https://doi.org/10.1016/j.cell.2023.04.031

Vancouver

Desai JV, Kumar D, Freiwald T, Chauss D, Johnson MD, Abers MS et al. C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection. CELL. 2023 Jun 22;186(13):2802-2822.e22. https://doi.org/10.1016/j.cell.2023.04.031

Bibtex

@article{6bad681059d643f6a62ff4b2b40a16ed,
title = "C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection",
abstract = "Systemic candidiasis is a common, high-mortality, nosocomial fungal infection. Unexpectedly, it has emerged as a complication of anti-complement C5-targeted monoclonal antibody treatment, indicating a critical niche for C5 in antifungal immunity. We identified transcription of complement system genes as the top biological pathway induced in candidemic patients and as predictive of candidemia. Mechanistically, C5a-C5aR1 promoted fungal clearance and host survival in a mouse model of systemic candidiasis by stimulating phagocyte effector function and ERK- and AKT-dependent survival in infected tissues. C5ar1 ablation rewired macrophage metabolism downstream of mTOR, promoting their apoptosis and enhancing mortality through kidney injury. Besides hepatocyte-derived C5, local C5 produced intrinsically by phagocytes provided a key substrate for antifungal protection. Lower serum C5a concentrations or a C5 polymorphism that decreases leukocyte C5 expression correlated independently with poor patient outcomes. Thus, local, phagocyte-derived C5 production licenses phagocyte antimicrobial function and confers innate protection during systemic fungal infection.",
author = "Desai, {Jigar V} and Dhaneshwar Kumar and Tilo Freiwald and Daniel Chauss and Johnson, {Melissa D} and Abers, {Michael S} and Steinbrink, {Julie M} and Perfect, {John R} and Barbara Alexander and Vasiliki Matzaraki and Snarr, {Brendan D} and Zarakas, {Marissa A} and Vasileios Oikonomou and Silva, {Lakmali M} and Raju Shivarathri and Emily Beltran and Demontel, {Luciana Negro} and Luopin Wang and Lim, {Jean K} and Dylan Launder and Conti, {Heather R} and Muthulekha Swamydas and McClain, {Micah T} and Moutsopoulos, {Niki M} and Majid Kazemian and Netea, {Mihai G} and Vinod Kumar and J{\"o}rg K{\"o}hl and Claudia Kemper and Behdad Afzali and Lionakis, {Michail S}",
note = "Published by Elsevier Inc.",
year = "2023",
month = jun,
day = "22",
doi = "10.1016/j.cell.2023.04.031",
language = "English",
volume = "186",
pages = "2802--2822.e22",
journal = "CELL",
issn = "0092-8674",
publisher = "Cell Press",
number = "13",

}

RIS

TY - JOUR

T1 - C5a-licensed phagocytes drive sterilizing immunity during systemic fungal infection

AU - Desai, Jigar V

AU - Kumar, Dhaneshwar

AU - Freiwald, Tilo

AU - Chauss, Daniel

AU - Johnson, Melissa D

AU - Abers, Michael S

AU - Steinbrink, Julie M

AU - Perfect, John R

AU - Alexander, Barbara

AU - Matzaraki, Vasiliki

AU - Snarr, Brendan D

AU - Zarakas, Marissa A

AU - Oikonomou, Vasileios

AU - Silva, Lakmali M

AU - Shivarathri, Raju

AU - Beltran, Emily

AU - Demontel, Luciana Negro

AU - Wang, Luopin

AU - Lim, Jean K

AU - Launder, Dylan

AU - Conti, Heather R

AU - Swamydas, Muthulekha

AU - McClain, Micah T

AU - Moutsopoulos, Niki M

AU - Kazemian, Majid

AU - Netea, Mihai G

AU - Kumar, Vinod

AU - Köhl, Jörg

AU - Kemper, Claudia

AU - Afzali, Behdad

AU - Lionakis, Michail S

N1 - Published by Elsevier Inc.

PY - 2023/6/22

Y1 - 2023/6/22

N2 - Systemic candidiasis is a common, high-mortality, nosocomial fungal infection. Unexpectedly, it has emerged as a complication of anti-complement C5-targeted monoclonal antibody treatment, indicating a critical niche for C5 in antifungal immunity. We identified transcription of complement system genes as the top biological pathway induced in candidemic patients and as predictive of candidemia. Mechanistically, C5a-C5aR1 promoted fungal clearance and host survival in a mouse model of systemic candidiasis by stimulating phagocyte effector function and ERK- and AKT-dependent survival in infected tissues. C5ar1 ablation rewired macrophage metabolism downstream of mTOR, promoting their apoptosis and enhancing mortality through kidney injury. Besides hepatocyte-derived C5, local C5 produced intrinsically by phagocytes provided a key substrate for antifungal protection. Lower serum C5a concentrations or a C5 polymorphism that decreases leukocyte C5 expression correlated independently with poor patient outcomes. Thus, local, phagocyte-derived C5 production licenses phagocyte antimicrobial function and confers innate protection during systemic fungal infection.

AB - Systemic candidiasis is a common, high-mortality, nosocomial fungal infection. Unexpectedly, it has emerged as a complication of anti-complement C5-targeted monoclonal antibody treatment, indicating a critical niche for C5 in antifungal immunity. We identified transcription of complement system genes as the top biological pathway induced in candidemic patients and as predictive of candidemia. Mechanistically, C5a-C5aR1 promoted fungal clearance and host survival in a mouse model of systemic candidiasis by stimulating phagocyte effector function and ERK- and AKT-dependent survival in infected tissues. C5ar1 ablation rewired macrophage metabolism downstream of mTOR, promoting their apoptosis and enhancing mortality through kidney injury. Besides hepatocyte-derived C5, local C5 produced intrinsically by phagocytes provided a key substrate for antifungal protection. Lower serum C5a concentrations or a C5 polymorphism that decreases leukocyte C5 expression correlated independently with poor patient outcomes. Thus, local, phagocyte-derived C5 production licenses phagocyte antimicrobial function and confers innate protection during systemic fungal infection.

U2 - 10.1016/j.cell.2023.04.031

DO - 10.1016/j.cell.2023.04.031

M3 - SCORING: Journal article

C2 - 37220746

VL - 186

SP - 2802-2822.e22

JO - CELL

JF - CELL

SN - 0092-8674

IS - 13

ER -