Mesenteric Th1 polarization and monocyte TNF‐α production: First steps to systemic inflammation in rats with cirrhosis†
Open accessAbstract
A systemic inflammatory state with increased circulating tumor necrosis factor alpha (TNF-alpha) has been related to the bacterial infection susceptibility and hemodynamic derangement of patients with cirrhosis. We compared the activation status of immune cell subpopulations defined by 4-color cytometry in mesenteric and peripheral lymph nodes and blood of rats with CCl(4)-cirrhosis to define the immune response initiation site, the T-cell and monocyte contribution to pro-inflammatory cytokine production, as well as the pathogenic role of enteric bacteria in the cirrhosis immune response. Th1 cells and monocytes were expanded in the mesenteric nodes (P < .001) and blood (P < .001) of rats with cirrhosis, and activated to produce interferon gamma (P < .0001) and TNF-alpha (P < .0001), respectively. The greater numbers of recently activated CD134(+) Th cells in mesenteric nodes compared with blood, the correlation between their numbers in mesenteric nodes and blood (r = 0.66, P < .001), and the expansion of activated CD45RC(-) Th cells, which are unable to re-enter lymph nodes, in mesenteric nodes but not in blood or axillary nodes points to mesenteric nodes as the origin site of activated Th cells. Abrogation of bacterial translocation by bowel decontamination reduced the number of activated Th cells and monocytes, and normalized interferon gamma production by Th cells and TNF-alpha production by monocytes in mesenteric nodes and blood, respectively. In conclusion, in cirrhosis, enteric bacteria start off an orchestrated immune response cascade in mesenteric nodes involving Th1 polarization and monocyte activation to TNF-alpha production. Later, the recirculation of these activated effector immune cells into blood promotes systemic inflammation.
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Increased TNF production by monocytes in mesenteric lymph nodes is one of the main factors increasing tight junction permeability.
“Increased production of TNF by monocytes in mesenteric lymph nodes constitutes one of the main factors increasing tight junction permeability145,146.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [145]
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- Authors
- Muñoz, L., Albillos, A., Nieto, M., Reyes, E., Lledó, L., Monserrat, J., Sanz, E., de la Hera, A., & Alvarez‐Mon, M.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Universidad de Alcalá (ES)
- Venue
- Hepatology
- Published
- 2005-08
- Volume
- 42
- Issue
- 2
- Pages
- 411-419
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2007240987
- Cited by
- 70
- References
- 29
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 1 · 2015: 7 · 2014: 2 · 2013: 2 · 2012: 5
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- e_Buah (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- liver cirrhosis, Th1 polarization, mesenteric lymph nodes, monocyte activation, TNF-α, interferon-gamma, bacterial translocation, systemic inflammation, CCl4-induced cirrhosis, enteric bacteria
- MeSH terms
- Animals, Inflammation, Interferon-gamma, Liver Cirrhosis, Experimental, Lymph Nodes, Male, Mesentery, Monocytes, Tumor Necrosis Factor-alpha, Cell Polarity, Rats, Sprague-Dawley, Th1 Cells, Rats
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