Involvement of TNF in limiting liver pathology and promoting parasite survival during schistosome infection

Davies, Stephen J.; Lim, K. C.; Blank, Rebecca B.; Kim, Jea-Hyoun; Lucas, Kimberley D.; Hernandez, David C; Sedgwick, Jonathon D.; McKerrow, James H.

doi:10.1016/j.ijpara.2003.10.010

Cited by 54 publications

(41 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a spontaneous mouse model of insulin-dependent diabetes mellitus, the NOD mouse, TNF led to increased [26,27] or attenuated [28][29][30] islet infiltration, depending on timing and duration of exposure of the immune system to TNF [11]. Indications for an immunoregulatory role for TNF have been also reported in mouse models of infectious diseases, such as in schistosome [31] and M. tuberculosis/BCG infections [32], where TNF was found to be required to limit immunopathologies in the liver and lung, respectively. In humans, anti-inflammatory effects of TNF may be responsible for the unexpected failure of treating patients with multiple sclerosis with a soluble TNFR1 fusion protein (lenercept) [33].…”

Section: Discussionmentioning

confidence: 87%

Soluble TNF‐α but not transmembrane TNF‐α sensitizes T cells for enhanced activation‐induced cell death

et al. 2009

View full text Add to dashboard Cite

In addition to its proinflammatory effects, TNF-a exhibits immunosuppression. Here, we compared the capacities of transmembrane TNF-a (tmTNF) and soluble TNF-a (sTNF) in regulating expansion of activated T cells by apoptosis. Splenic CD4 1 T cells from wtTNF, TNF-a-deficient (TNF À/À ) and TNF À/À mice expressing a non-cleavable mutant tmTNF showed comparable proliferation rates upon TCR-mediated stimulation. Activationinduced cell death (AICD), however, was significantly attenuated in tmTNF and TNF À/À , compared with wtTNF CD4 1 T cells. Addition of sTNF during initial priming was sufficient to enhance susceptibility to AICD in tmTNF and TNF À/À CD4 1 T cells to levels seen in wtTNF CD4 1 T cells, whereas addition of sTNF only during restimulation failed to enhance AICD. sTNF-induced, enhanced susceptibility to AICD was dependent on both TNF receptors. The reduced susceptibility of tmTNF CD4 1 T cells for AICD was also evident in an in vivo model of adoptively transferred CD4 1 T-cell-mediated colonic inflammation. Hence, the presence of sTNF during T-cell priming may represent an important mechanism to sensitize activated T cells for apoptosis, thereby attenuating the extent and duration of T-cell reactivities and subsequent T-cell-mediated, excessive inflammation.Key words: Activation-induced cell death . CD4 1 T cells . Colitis . TNF-a .Transmembrane TNF IntroductionTNF is a pleiotropic cytokine involved in innate and adaptive immunity. It is regarded as the prototypic proinflammatory cytokine and is crucial in immune defense against many pathogens but also during development of various autoimmune diseases [1]. The type I transmembrane 26 kDa precursor TNF molecule (tmTNF) is preferentially cleaved by the extracellular metalloproteinase TNF-a-converting-enzyme (TACE) to release trimers of the 17 kDa soluble form (sTNF) [2]. The generation of non-cleavable mutants of TNF revealed that tmTNF and sTNF exert distinct biological functions. A main function ascribed to tmTNF is the induction of cell death [3]. Some of the proinflammatory effects ascribed to TNF are also mediated by tmTNF as shown by the tmTNF-induced up-regulation of ICAM-1 and VCAM-1 on endothelial cells in vitro [4]. Mice overexpressing a non-cleavable tmTNF mutein are prone to develop arthritis [5] and signs of hepatitis after Concanavalin A (Con A) administration [6]. tmTNF transgenic mice [4] and tmTNF knock-in mice [7] are, in contrast to wtTNF mice, protected from LPS-induced death, thus demonstrating the distinct roles exerted by tmTNF and secreted TNF. Treatment of mice with a synthetic TACE inhibitor also protects mice from endotoxin-mediated death [8], indicating that TACE may represent a target to prevent the fatal effects of excessive sTNF production while maintaining the local TNF-mediated effects required in the host response against intracellular pathogens. The fact that tmTNF mice, but not TNF-deficient mice, are still capable of forming granulomas following infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG) and thu...

show abstract

Section: Discussionmentioning

confidence: 87%

Soluble TNF‐α but not transmembrane TNF‐α sensitizes T cells for enhanced activation‐induced cell death

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Eosinophils can cause parasite damage in S. mansoni and other worm infections in vitro (26) and in vivo (34). Nevertheless, mice selectively deficient in eosinophils (31) or in IL-5, which causes a profound reduction of eosinophils, control parasite burden as efficiently as wild-type mice (28,30).…”

Section: Discussionmentioning

confidence: 99%

Macrophage migration inhibitory factor is critical to interleukin‐5‐driven eosinophilopoiesis and tissue eosinophilia triggered by Schistosoma mansoni infection

Magalhães¹,

Paiva²,

Souza³

et al. 2008

FASEB j.

View full text Add to dashboard Cite

Macrophage migration inhibitory factor (MIF) participates in the pathogenesis of inflammatory diseases, including asthma, in which it enhances airway hypersensitivity and tissue eosinophilia. Herein, we investigated the role of MIF in eosinophilopoiesis and tissue eosinophilia using Schistosoma mansoni infection. MIF-deficient (Mif(-/-)) mice had similar numbers of adult worms, eggs, and granulomas compared to wild-type mice, but the size of granulomas was strikingly reduced due to smaller numbers of eosinophils. MIF did not affect the acquired response to infection, as Mif(-/-) mice produced normal amounts of Th2 cytokines and IgE. Nevertheless, recombinant MIF (rMIF) behaved as a chemoattractant for eosinophils, what could partially explain the reduced eosinophilia in infected Mif(-/-) mice. Moreover, the percentage of eosinophils was reduced in bone marrows of Mif(-/-) mice chronically infected with S. mansoni compared to wild type. Mif(-/-) had impaired eosinophilopoiesis in response to interleukin (IL)-5 and addition of rMIF to bone marrow cultures from IL-5 transgenic mice enhanced the generation of eosinophils. In the absence of MIF, eosinophil precursors were unable to survive the IL-5-supplemented cell culture, and were ingested by macrophages. Treatment with pancaspase inhibitor z-VAD or rMIF promoted the survival of eosinophil progenitors. Together, these results indicate that MIF participates in IL-5-driven maturation of eosinophils and in tissue eosinophilia associated with S. mansoni infection.

show abstract

“…This process also indirectly induces the production of other fibrogenic factors, such IL-1 and IL-6 (Kimura et al 2003). Moreover, Davies et al (2004) have reported that TNF-α essentially functions as a trophic factor for maintaining the viability of adult Schistosoma worms, in addition to its role as a mitogen and promoter of tumour development in schistosomiasis-associated carcinoma (Balkwill et al 2006).…”

Section: Resultsmentioning

confidence: 99%

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients

Hamed

Ahmed

Khaled

2011

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

Involvement of TNF in limiting liver pathology and promoting parasite survival during schistosome infection

Cited by 54 publications

References 38 publications

Soluble TNF‐α but not transmembrane TNF‐α sensitizes T cells for enhanced activation‐induced cell death

Soluble TNF‐α but not transmembrane TNF‐α sensitizes T cells for enhanced activation‐induced cell death

Macrophage migration inhibitory factor is critical to interleukin‐5‐driven eosinophilopoiesis and tissue eosinophilia triggered by Schistosoma mansoni infection

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients

Contact Info

Product

Resources

About