Compartmentalization of Immune Response and Microbial Translocation in Decompensated Cirrhosis

Camila Alvarez-Silva, Robert Schierwagen, Alessandra Pohlmann, Fernando Magdaleno, Frank E. Uschner, Patrick Ryan, Maria J.G.T. Vehreschild, Joan Claria, Eicke Latz, Benjamin Lelouvier, Manimozhiyan Arumugam, Jonel Trebicka

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Background: Acquired dysfunctional immunity in cirrhosis predisposes patients to frequent bacterial infections, especially spontaneous bacterial peritonitis (SBP), leading to systemic inflammation that is associated with poor outcome. But systemic inflammation can also be found in the absence of a confirmed infection. Detection of bacterial DNA has been investigated as a marker of SBP and as a predictor of prognosis. Data is, however, contradictory. Here we investigated whether levels of IL-6 and IL-8 putatively produced by myeloid cells in ascites are associated with systemic inflammation and whether inflammation depends on the presence of specific bacterial DNA. Methods and Materials: We enrolled 33 patients with decompensated liver cirrhosis from whom we collected paired samples of blood and ascites. IL-6 and IL-8 were measured in serum samples of all patients using ELISA. In a subset of 10 representative patients, bacterial DNA was extracted from ascites and whole blood, followed by 16S rRNA gene amplicon sequencing. Results: There were significantly higher levels of IL-6 in ascites fluid compared to blood samples in all patients. Interestingly, IL-6 levels in blood correlated tightly with disease severity and surrogates of systemic inflammation, while IL-6 levels in ascites did not. Moreover, patients with higher blood CRP levels showed greater SBP prevalence compared to patients with lower levels, despite similar positive culture results. Bacterial richness was also significantly higher in ascites compared to the corresponding patient blood. We identified differences in microbial composition and diversity between ascites and blood, but no tight relationship with surrogates of systemic inflammation could be observed. Discussion: In decompensated cirrhosis, markers of systemic inflammation and microbiota composition seem to be dysregulated in ascites and blood. While a relationship between systemic inflammation and microbiota composition seems to exist in blood, this is not the case for ascites in our hands. These data may suggest compartmentalization of the immune response and interaction of the latter with the microbiota especially in the blood compartment.

OriginalsprogEngelsk
Artikelnummer69
TidsskriftFrontiers in Immunology
Vol/bind10
Udgave nummerFEB
Antal sider11
ISSN1664-3224
DOI
StatusUdgivet - feb. 2019

Fingeraftryk

Interleukin-6
Bacterial DNA
Microbiota
Interleukin-8
Patient Advocacy
Myeloid Cells
rRNA Genes
Liver Cirrhosis
Serum

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Alvarez-Silva, C., Schierwagen, R., Pohlmann, A., Magdaleno, F., Uschner, F. E., Ryan, P., ... Trebicka, J. (2019). Compartmentalization of Immune Response and Microbial Translocation in Decompensated Cirrhosis. Frontiers in Immunology, 10(FEB), [69]. https://doi.org/10.3389/fimmu.2019.00069
Alvarez-Silva, Camila ; Schierwagen, Robert ; Pohlmann, Alessandra ; Magdaleno, Fernando ; Uschner, Frank E. ; Ryan, Patrick ; Vehreschild, Maria J.G.T. ; Claria, Joan ; Latz, Eicke ; Lelouvier, Benjamin ; Arumugam, Manimozhiyan ; Trebicka, Jonel. / Compartmentalization of Immune Response and Microbial Translocation in Decompensated Cirrhosis. I: Frontiers in Immunology. 2019 ; Bind 10, Nr. FEB.
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title = "Compartmentalization of Immune Response and Microbial Translocation in Decompensated Cirrhosis",
abstract = "Background: Acquired dysfunctional immunity in cirrhosis predisposes patients to frequent bacterial infections, especially spontaneous bacterial peritonitis (SBP), leading to systemic inflammation that is associated with poor outcome. But systemic inflammation can also be found in the absence of a confirmed infection. Detection of bacterial DNA has been investigated as a marker of SBP and as a predictor of prognosis. Data is, however, contradictory. Here we investigated whether levels of IL-6 and IL-8 putatively produced by myeloid cells in ascites are associated with systemic inflammation and whether inflammation depends on the presence of specific bacterial DNA. Methods and Materials: We enrolled 33 patients with decompensated liver cirrhosis from whom we collected paired samples of blood and ascites. IL-6 and IL-8 were measured in serum samples of all patients using ELISA. In a subset of 10 representative patients, bacterial DNA was extracted from ascites and whole blood, followed by 16S rRNA gene amplicon sequencing. Results: There were significantly higher levels of IL-6 in ascites fluid compared to blood samples in all patients. Interestingly, IL-6 levels in blood correlated tightly with disease severity and surrogates of systemic inflammation, while IL-6 levels in ascites did not. Moreover, patients with higher blood CRP levels showed greater SBP prevalence compared to patients with lower levels, despite similar positive culture results. Bacterial richness was also significantly higher in ascites compared to the corresponding patient blood. We identified differences in microbial composition and diversity between ascites and blood, but no tight relationship with surrogates of systemic inflammation could be observed. Discussion: In decompensated cirrhosis, markers of systemic inflammation and microbiota composition seem to be dysregulated in ascites and blood. While a relationship between systemic inflammation and microbiota composition seems to exist in blood, this is not the case for ascites in our hands. These data may suggest compartmentalization of the immune response and interaction of the latter with the microbiota especially in the blood compartment.",
keywords = "acute-on-chronic liver failure, ascites, cirrhosis, cytokines, microbiome, myeloid cells, systemic inflammation",
author = "Camila Alvarez-Silva and Robert Schierwagen and Alessandra Pohlmann and Fernando Magdaleno and Uschner, {Frank E.} and Patrick Ryan and Vehreschild, {Maria J.G.T.} and Joan Claria and Eicke Latz and Benjamin Lelouvier and Manimozhiyan Arumugam and Jonel Trebicka",
year = "2019",
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Alvarez-Silva, C, Schierwagen, R, Pohlmann, A, Magdaleno, F, Uschner, FE, Ryan, P, Vehreschild, MJGT, Claria, J, Latz, E, Lelouvier, B, Arumugam, M & Trebicka, J 2019, 'Compartmentalization of Immune Response and Microbial Translocation in Decompensated Cirrhosis', Frontiers in Immunology, bind 10, nr. FEB, 69. https://doi.org/10.3389/fimmu.2019.00069

Compartmentalization of Immune Response and Microbial Translocation in Decompensated Cirrhosis. / Alvarez-Silva, Camila; Schierwagen, Robert; Pohlmann, Alessandra; Magdaleno, Fernando; Uschner, Frank E.; Ryan, Patrick; Vehreschild, Maria J.G.T.; Claria, Joan; Latz, Eicke; Lelouvier, Benjamin; Arumugam, Manimozhiyan; Trebicka, Jonel.

I: Frontiers in Immunology, Bind 10, Nr. FEB, 69, 02.2019.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Compartmentalization of Immune Response and Microbial Translocation in Decompensated Cirrhosis

AU - Alvarez-Silva, Camila

AU - Schierwagen, Robert

AU - Pohlmann, Alessandra

AU - Magdaleno, Fernando

AU - Uschner, Frank E.

AU - Ryan, Patrick

AU - Vehreschild, Maria J.G.T.

AU - Claria, Joan

AU - Latz, Eicke

AU - Lelouvier, Benjamin

AU - Arumugam, Manimozhiyan

AU - Trebicka, Jonel

PY - 2019/2

Y1 - 2019/2

N2 - Background: Acquired dysfunctional immunity in cirrhosis predisposes patients to frequent bacterial infections, especially spontaneous bacterial peritonitis (SBP), leading to systemic inflammation that is associated with poor outcome. But systemic inflammation can also be found in the absence of a confirmed infection. Detection of bacterial DNA has been investigated as a marker of SBP and as a predictor of prognosis. Data is, however, contradictory. Here we investigated whether levels of IL-6 and IL-8 putatively produced by myeloid cells in ascites are associated with systemic inflammation and whether inflammation depends on the presence of specific bacterial DNA. Methods and Materials: We enrolled 33 patients with decompensated liver cirrhosis from whom we collected paired samples of blood and ascites. IL-6 and IL-8 were measured in serum samples of all patients using ELISA. In a subset of 10 representative patients, bacterial DNA was extracted from ascites and whole blood, followed by 16S rRNA gene amplicon sequencing. Results: There were significantly higher levels of IL-6 in ascites fluid compared to blood samples in all patients. Interestingly, IL-6 levels in blood correlated tightly with disease severity and surrogates of systemic inflammation, while IL-6 levels in ascites did not. Moreover, patients with higher blood CRP levels showed greater SBP prevalence compared to patients with lower levels, despite similar positive culture results. Bacterial richness was also significantly higher in ascites compared to the corresponding patient blood. We identified differences in microbial composition and diversity between ascites and blood, but no tight relationship with surrogates of systemic inflammation could be observed. Discussion: In decompensated cirrhosis, markers of systemic inflammation and microbiota composition seem to be dysregulated in ascites and blood. While a relationship between systemic inflammation and microbiota composition seems to exist in blood, this is not the case for ascites in our hands. These data may suggest compartmentalization of the immune response and interaction of the latter with the microbiota especially in the blood compartment.

AB - Background: Acquired dysfunctional immunity in cirrhosis predisposes patients to frequent bacterial infections, especially spontaneous bacterial peritonitis (SBP), leading to systemic inflammation that is associated with poor outcome. But systemic inflammation can also be found in the absence of a confirmed infection. Detection of bacterial DNA has been investigated as a marker of SBP and as a predictor of prognosis. Data is, however, contradictory. Here we investigated whether levels of IL-6 and IL-8 putatively produced by myeloid cells in ascites are associated with systemic inflammation and whether inflammation depends on the presence of specific bacterial DNA. Methods and Materials: We enrolled 33 patients with decompensated liver cirrhosis from whom we collected paired samples of blood and ascites. IL-6 and IL-8 were measured in serum samples of all patients using ELISA. In a subset of 10 representative patients, bacterial DNA was extracted from ascites and whole blood, followed by 16S rRNA gene amplicon sequencing. Results: There were significantly higher levels of IL-6 in ascites fluid compared to blood samples in all patients. Interestingly, IL-6 levels in blood correlated tightly with disease severity and surrogates of systemic inflammation, while IL-6 levels in ascites did not. Moreover, patients with higher blood CRP levels showed greater SBP prevalence compared to patients with lower levels, despite similar positive culture results. Bacterial richness was also significantly higher in ascites compared to the corresponding patient blood. We identified differences in microbial composition and diversity between ascites and blood, but no tight relationship with surrogates of systemic inflammation could be observed. Discussion: In decompensated cirrhosis, markers of systemic inflammation and microbiota composition seem to be dysregulated in ascites and blood. While a relationship between systemic inflammation and microbiota composition seems to exist in blood, this is not the case for ascites in our hands. These data may suggest compartmentalization of the immune response and interaction of the latter with the microbiota especially in the blood compartment.

KW - acute-on-chronic liver failure

KW - ascites

KW - cirrhosis

KW - cytokines

KW - microbiome

KW - myeloid cells

KW - systemic inflammation

U2 - 10.3389/fimmu.2019.00069

DO - 10.3389/fimmu.2019.00069

M3 - Journal article

VL - 10

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - FEB

M1 - 69

ER -

Alvarez-Silva C, Schierwagen R, Pohlmann A, Magdaleno F, Uschner FE, Ryan P et al. Compartmentalization of Immune Response and Microbial Translocation in Decompensated Cirrhosis. Frontiers in Immunology. 2019 feb;10(FEB). 69. https://doi.org/10.3389/fimmu.2019.00069