A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection. / Papareddy, Praveen; Rossnagel, Madlen; Doreen Hollwedel, Femke; Kilic, Gülcan; Veerla, Srinivas; Naudin, Clément; Smeds, Emanuel; Westman, Johannes; Martinez-Martinez, Irene; Egesten, Arne; de la Morena-Barrio, Maria Eugenia; Corral, Javier; Linder, Adam; Artoni, Andrea; Abbattista, Maria; Novembrino, Cristina; Herbert Brakebusch, Cord; Martinelli, Ida; Kasetty, Gopinath; Herwald, Heiko.

In: Nature Microbiology, Vol. 4, No. 12, 2019, p. 2442-2455.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Papareddy, P, Rossnagel, M, Doreen Hollwedel, F, Kilic, G, Veerla, S, Naudin, C, Smeds, E, Westman, J, Martinez-Martinez, I, Egesten, A, de la Morena-Barrio, ME, Corral, J, Linder, A, Artoni, A, Abbattista, M, Novembrino, C, Herbert Brakebusch, C, Martinelli, I, Kasetty, G & Herwald, H 2019, 'A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection', Nature Microbiology, vol. 4, no. 12, pp. 2442-2455. https://doi.org/10.1038/s41564-019-0559-6

APA

Papareddy, P., Rossnagel, M., Doreen Hollwedel, F., Kilic, G., Veerla, S., Naudin, C., Smeds, E., Westman, J., Martinez-Martinez, I., Egesten, A., de la Morena-Barrio, M. E., Corral, J., Linder, A., Artoni, A., Abbattista, M., Novembrino, C., Herbert Brakebusch, C., Martinelli, I., Kasetty, G., & Herwald, H. (2019). A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection. Nature Microbiology, 4(12), 2442-2455. https://doi.org/10.1038/s41564-019-0559-6

Vancouver

Papareddy P, Rossnagel M, Doreen Hollwedel F, Kilic G, Veerla S, Naudin C et al. A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection. Nature Microbiology. 2019;4(12):2442-2455. https://doi.org/10.1038/s41564-019-0559-6

Author

Papareddy, Praveen ; Rossnagel, Madlen ; Doreen Hollwedel, Femke ; Kilic, Gülcan ; Veerla, Srinivas ; Naudin, Clément ; Smeds, Emanuel ; Westman, Johannes ; Martinez-Martinez, Irene ; Egesten, Arne ; de la Morena-Barrio, Maria Eugenia ; Corral, Javier ; Linder, Adam ; Artoni, Andrea ; Abbattista, Maria ; Novembrino, Cristina ; Herbert Brakebusch, Cord ; Martinelli, Ida ; Kasetty, Gopinath ; Herwald, Heiko. / A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection. In: Nature Microbiology. 2019 ; Vol. 4, No. 12. pp. 2442-2455.

Bibtex

@article{a13a39292c8e4f47a40e249f562a0873,
title = "A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection",
abstract = "Severe infectious diseases are often characterized by an overwhelming and unbalanced systemic immune response to microbial infections. Human antithrombin (hAT) is a crucial coagulation inhibitor with anti-inflammatory activities. Here we identify three hAT-binding proteins (CD13, CD300f and LRP-1) on human monocytes that are involved in blocking the activity of nuclear factor-κB. We found that the modulating effect is primarily restricted to the less abundant β-isoform (hβAT) of hAT that lacks N-glycosylation at position 135. Individuals with a mutation at this position have increased production of hβAT and analysis of their blood, which was stimulated ex vivo with lipopolysaccharide, showed a decreased inflammatory response. Similar findings were recorded when heterozygotic mice expressing hAT or hβAT were challenged with lipopolysaccharide or infected with Escherichia coli bacteria. Our results finally demonstrate that in a lethal E. coli infection model, survival rates increased when mice were treated with hβAT one hour and five hours after infection. The treatment also resulted in a reduction of the inflammatory response and less severe organ damage.",
author = "Praveen Papareddy and Madlen Rossnagel and {Doreen Hollwedel}, Femke and G{\"u}lcan Kilic and Srinivas Veerla and Cl{\'e}ment Naudin and Emanuel Smeds and Johannes Westman and Irene Martinez-Martinez and Arne Egesten and {de la Morena-Barrio}, {Maria Eugenia} and Javier Corral and Adam Linder and Andrea Artoni and Maria Abbattista and Cristina Novembrino and {Herbert Brakebusch}, Cord and Ida Martinelli and Gopinath Kasetty and Heiko Herwald",
year = "2019",
doi = "10.1038/s41564-019-0559-6",
language = "English",
volume = "4",
pages = "2442--2455",
journal = "Nature Microbiology",
issn = "2058-5276",
publisher = "nature publishing group",
number = "12",

}

RIS

TY - JOUR

T1 - A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection

AU - Papareddy, Praveen

AU - Rossnagel, Madlen

AU - Doreen Hollwedel, Femke

AU - Kilic, Gülcan

AU - Veerla, Srinivas

AU - Naudin, Clément

AU - Smeds, Emanuel

AU - Westman, Johannes

AU - Martinez-Martinez, Irene

AU - Egesten, Arne

AU - de la Morena-Barrio, Maria Eugenia

AU - Corral, Javier

AU - Linder, Adam

AU - Artoni, Andrea

AU - Abbattista, Maria

AU - Novembrino, Cristina

AU - Herbert Brakebusch, Cord

AU - Martinelli, Ida

AU - Kasetty, Gopinath

AU - Herwald, Heiko

PY - 2019

Y1 - 2019

N2 - Severe infectious diseases are often characterized by an overwhelming and unbalanced systemic immune response to microbial infections. Human antithrombin (hAT) is a crucial coagulation inhibitor with anti-inflammatory activities. Here we identify three hAT-binding proteins (CD13, CD300f and LRP-1) on human monocytes that are involved in blocking the activity of nuclear factor-κB. We found that the modulating effect is primarily restricted to the less abundant β-isoform (hβAT) of hAT that lacks N-glycosylation at position 135. Individuals with a mutation at this position have increased production of hβAT and analysis of their blood, which was stimulated ex vivo with lipopolysaccharide, showed a decreased inflammatory response. Similar findings were recorded when heterozygotic mice expressing hAT or hβAT were challenged with lipopolysaccharide or infected with Escherichia coli bacteria. Our results finally demonstrate that in a lethal E. coli infection model, survival rates increased when mice were treated with hβAT one hour and five hours after infection. The treatment also resulted in a reduction of the inflammatory response and less severe organ damage.

AB - Severe infectious diseases are often characterized by an overwhelming and unbalanced systemic immune response to microbial infections. Human antithrombin (hAT) is a crucial coagulation inhibitor with anti-inflammatory activities. Here we identify three hAT-binding proteins (CD13, CD300f and LRP-1) on human monocytes that are involved in blocking the activity of nuclear factor-κB. We found that the modulating effect is primarily restricted to the less abundant β-isoform (hβAT) of hAT that lacks N-glycosylation at position 135. Individuals with a mutation at this position have increased production of hβAT and analysis of their blood, which was stimulated ex vivo with lipopolysaccharide, showed a decreased inflammatory response. Similar findings were recorded when heterozygotic mice expressing hAT or hβAT were challenged with lipopolysaccharide or infected with Escherichia coli bacteria. Our results finally demonstrate that in a lethal E. coli infection model, survival rates increased when mice were treated with hβAT one hour and five hours after infection. The treatment also resulted in a reduction of the inflammatory response and less severe organ damage.

U2 - 10.1038/s41564-019-0559-6

DO - 10.1038/s41564-019-0559-6

M3 - Journal article

C2 - 31548687

AN - SCOPUS:85074049504

VL - 4

SP - 2442

EP - 2455

JO - Nature Microbiology

JF - Nature Microbiology

SN - 2058-5276

IS - 12

ER -

ID: 230149112