A leukotriene-dependent spleen-liver axis drives TNF production in systemic inflammation

Fonseca, Monique T.; Moretti, Eduardo Hermógenes; Marques, Lucas Maciel Mauriz; Machado, Bianca F.; Brito, Camila F.; Guedes, Jady; Komegae, Evilin Naname; Vieira, Thayna S.; Festuccia, William T.; Lopes, Norberto P.; Steiner, Alexandre A.

doi:10.1126/scisignal.abb0969

Cited by 29 publications

(16 citation statements)

References 50 publications

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“…Cagnina et al, recently showed excess TNF production in a CGD mouse model challenged with Aspergillus triggers additional neutrophil recruitment, driving a pro-inflammatory spiral which is responsible for host lung damage [ 41 ]. This supports other research demonstrating exaggerated TNF responses are responsible for host injury [ 163 , 164 ]. ROS are believed to inhibit NF-κB signalling to prevent hyper-inflammation [ 165 , 166 ].…”

Section: Failures Of Innate Immunity In Diseasesupporting

confidence: 91%

A Fun-Guide to Innate Immune Responses to Fungal Infections

Burgess

Condliffe²,

Elks³

2022

JoF

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Immunocompromised individuals are at high risk of developing severe fungal infections with high mortality rates, while fungal pathogens pose little risk to most healthy people. Poor therapeutic outcomes and growing antifungal resistance pose further challenges for treatments. Identifying specific immunomodulatory mechanisms exploited by fungal pathogens is critical for our understanding of fungal diseases and development of new therapies. A gap currently exists between the large body of literature concerning the innate immune response to fungal infections and the potential manipulation of host immune responses to aid clearance of infection. This review considers the innate immune mechanisms the host deploys to prevent fungal infection and how these mechanisms fail in immunocompromised hosts. Three clinically relevant fungal pathogens (Candida albicans, Cryptococcus spp. and Aspergillus spp.) will be explored. This review will also examine potential mechanisms of targeting the host therapeutically to improve outcomes of fungal infection.

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Section: Failures Of Innate Immunity In Diseasesupporting

confidence: 91%

A Fun-Guide to Innate Immune Responses to Fungal Infections

Burgess

Condliffe²,

Elks³

2022

JoF

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“…Some studies have also shown that the spleen participates in the mucosal immune response in the gut [ 22 , 23 ]. Because intestinal and splenic blood flow forms the portal vein system passing into the liver, the antigens and inflammatory factors from intestinal and splenic blood can enter the liver [ 24 , 25 ]. In addition, the gut and liver communicate via a tight bidirectional connection through the biliary tract [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Inflammatory response of gut, spleen, and liver in mice induced by orally administeredPorphyromonas gingivalis

Liu

Huang

et al. 2022

Journal of Oral Microbiology

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Background Periodontitis is a chronic multifactorial inflammatory disease. Porphyromonas gingivalis is a primary periopathogen in the initiation and development of periodontal disease. Evidence has shown that P. gingivalis is associated with systemic diseases, including IBD and fatty liver disease. Inflammatory response is a key feature of diseases related to this species. Methods C57BL/6 mice were administered either PBS, or P. gingivalis . After 9 weeks, the inflammatory response in gut, spleen, and liver was analyzed. Results The findings revealed significant disturbance of the intestinal microbiota and increased inflammatory factors in the gut of P. gingivalis -administered mice. Administrated P. gingivalis remarkably promoted the secretion of IRF-1 and activated the inflammatory pathway IFN-γ/STAT1 in the spleen. Histologically, mice treated with P. gingivalis exhibited hepatocyte damage and lipid deposition. The inflammatory factors IL-17a, IL-6, and ROR-γt were also upregulated in the liver of mice fed with P. gingivalis . Lee’s index, spleen index, and liver index were also increased. Conclusion These results suggest that administrated P. gingivalis evokes inflammation in gut, spleen, and liver, which might promote the progression of various systemic diseases.

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“…28 It is noteworthy that splenic macrophage-derived leukotriene B4 enhances TNF-α secretion by hepatic Kupffer cells through the portal vein, and that splenectomy inhibits LPS-induced expression of TNF-α in the liver. 29 These findings indicate that spleen-derived humoral factors strongly contribute to the regulation of hepatic inflammation, and that cytokines released by splenic cells may be involved in NASH development.…”

Section: Discussionmentioning

confidence: 86%

Iron-accumulating splenocytes may exacerbate non-alcoholic steatohepatitis through the production of proinflammatory cytokines and reactive oxygen species

Murotomi

Tawara

Sutoh

et al. 2022

Exp Biol Med (Maywood)

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Non-alcoholic steatohepatitis (NASH) results from non-alcoholic fatty liver disease (NAFLD) via multiple-parallel events, including hepatic triglyceride accumulation, oxidative stress, and inflammation. The complex interaction between the liver and multiple other organs is involved in NASH development. Although spleen-derived humoral factors can directly contribute to NAFLD/NASH onset via the portal vein, the status of the spleen in the early stage of NASH remains unknown. Here, our aim was to investigate whether splenocytes may exacerbate NASH via the generations of reactive oxygen species (ROS) and proinflammatory cytokines. Iron accumulation was observed in the spleen but not the liver, and the proportion of phagocytic macrophages increased in the spleen of Tsumura Suzuki Obese Diabetes (TSOD) mice showing histological characteristics of NASH in the early stage. The splenocytes generated moderate amounts of ROS and released high amounts of tumor necrosis factor (TNF)-α in response to lipopolysaccharide, indicating excessive inflammatory cytokine released by activated macrophages in iron-accumulating spleens. Our results suggest that iron-accumulating splenocytes can easily induce inflammation and contribute to exacerbate NASH via the portal vein. Thus, the regulation of iron metabolism in the spleen should be considered in the development of novel therapeutic targets against NASH.

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A leukotriene-dependent spleen-liver axis drives TNF production in systemic inflammation

Cited by 29 publications

References 50 publications

A Fun-Guide to Innate Immune Responses to Fungal Infections

A Fun-Guide to Innate Immune Responses to Fungal Infections

Inflammatory response of gut, spleen, and liver in mice induced by orally administeredPorphyromonas gingivalis

Iron-accumulating splenocytes may exacerbate non-alcoholic steatohepatitis through the production of proinflammatory cytokines and reactive oxygen species

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