Tumor Necrosis Factor (TNF) Receptor—1 (TNFp55) Signal Transduction and Macrophage-Derived Soluble TNF Are Crucial for Nitric Oxide—Mediated Trypanosoma congolense Parasite Killing

Magez, Stefan; Radwanska, Magdalena; Drennan, Michael; Fick, Lizette; Baral, Toya Nath; Allie, Nasiema; Jacobs, Muazzam; Nedospasov, Sergei; Brombacher, Frank; Ryffel, Bernard; de Baetselier, Patrick
September 2007
Journal of Infectious Diseases;9/15/2007, Vol. 196 Issue 6, p954
Academic Journal
Control of Trypanosoma congolense infections requires an early cell-mediated immune response. To unravel the role of tumor necrosis factor (TNF) in this process, 6 different T. congolense strains were used in 6 different gene-deficient mouse models that included TNF-/-, TNF receptor—1 (TNFp55)-/-, and TNF receptor—2 (TNFp75)-/- mice, 2 cell type—specific TNF-/- mice, as well as TNF—knock-in mice that expressed only membrane-bound TNF. Our results indicate that soluble TNF produced by macrophages/neutrophils and TNFp55 signaling are essential and sufficient to control arasitemia. The downstream mechanism in the control of T. congolense infection depends on inducible nitric oxide synthase activation in the liver. Such a role for nitric oxide is corroborated ex vivo, because the inhibitor NG-monomethyl-L-arginine blocks the trypanolytic activity of the adherent liver cell population, whereas exogenous interferon-γ that stimulates nitric oxide production enhances parasite killing. In conclusion, the control of T. congolense infection depends on macrophage/neutrophil-derived soluble TNF and intact TNFp55 signaling, which induces trypanolytic nitric oxide.


Related Articles

  • CD40 Is Essential in the Upregulation of TRAF Proteins and NF-KappaB-Dependent Proinflammatory Gene Expression after Arterial Injury. Song, Zifang; Jin, Rong; Shiyong Yu; Rivet, Joshua J.; Smyth, Susan S.; Nanda, Anil; Granger, D. Neil; Guohong Li // PLoS ONE;2011, Vol. 6 Issue 8, p1 

    Despite extensive investigations, restenosis, which is characterized primarily by neointima formation, remains an unsolved clinical problem after vascular interventions. A recent study has shown that CD40 signaling through TNF receptor associated factor 6 (TRAF6) plays a key role in neointima...

  • Altered Cytokine and Nitric Oxide Secretion In Vitro by Macrophages From Diabetic Type II-Like db/db Mice. Zykova, Svetlana N.; Jenssen, Trond G.; Berdal, Margrete; Olsen, Randi; Myklebust, Reidar; Seljelid, Rolf // Diabetes;Sep2000, Vol. 49 Issue 9, p1451 

    Studies the mechanics of macrophage dysfunction in human diabetes using type 2 db-db mice. Comparison of levels of tumor necrosis factor alpha and interleukin-1beta levels in diabetic versus control animals; High nitric oxide production; Altered morphological appearance of macrophages in diabetics.

  • Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity. Shiow-Yunn Sheu; Yi-Wen Hong; Jui-Sheng Sun; Man-Hai Liu; Ching-Yun Chen; Cherng-Jyh Ke // BMC Complementary & Alternative Medicine;9/17/2015, Vol. 15 Issue 1, p324 

    Background: Hypoxia could lead to microglia activation and inflammatory mediators’ overproduction. These inflammatory molecules could amplify the neuroinflammatory process and exacerbate neuronal injury. The aim of this study is to find out whether harpagoside could reduce hypoxia-induced...

  • Gng12 is a novel negative regulator of LPS-induced inflammation in the microglial cell line BV-2. Kelley Larson; Michael Draper; Maciej Lipko; Michal Dabrowski // Inflammation Research;Jan2010, Vol. 59 Issue 1, p15 

    Abstract Background  Inflammation plays a central role in many neurodegenerative diseases, including Parkinson’s, Alzheimer’s, multiple sclerosis, amyotrophic lateral sclerosis, and AIDS dementia. Microglia are the resident macrophages of the central nervous system and are...

  • Role of CCL19/21 and its possible signaling through CXCR3 in development of metallophilic macrophages in the mouse thymus. Milićević, Novica; Miljković, Miloš; Milićević, Živana; Labudović-Borović, Milica; Wang, Xiaoping; Laan, Martti; Peterson, Pärt; Randall, Troy; Westermann, Jürgen // Histochemistry & Cell Biology;Jun2011, Vol. 135 Issue 6, p593 

    We have already shown that metallophilic macrophages, which represent an important component in the thymus physiology, are lacking in lymphotoxin-β receptor-deficient mice. However, further molecular requirements for the development and correct tissue positioning of these cells are unknown....

  • Soluble Calreticulin Induces Tumor Necrosis Factor-α (TNF-α) and Interleukin (IL)-6 Production by Macrophages through Mitogen-Activated Protein Kinase (MAPK) and NFκB Signaling Pathways. Cui-Cui Duo; Fang-Yuan Gong; Xiao-Yan He; Yan-Mei Li; Jun Wang; Jin-Ping Zhang; Xiao-Ming Gao // International Journal of Molecular Sciences;Feb2014, Vol. 15 Issue 2, p2916 

    We have recently reported that soluble calreticulin (CRT) accumulates in the sera of patients with rheumatoid arthritis or systemic lupus erythematosus. Moreover, following self-oligomerization, soluble recombinant CRT (rCRT) polypeptides exhibit potent immunostimulatory activities including...

  • Tristetraprolin Mediates Radiation-Induced TNF-α Production in Lung Macrophages. Ray, Dipankar; Shukla, Shirish; Allam, Uday Sankar; Helman, Abigail; Ramanand, Susmita Gurjar; Tran, Linda; Bassetti, Michael; Krishnamurthy, Pranathi Meda; Rumschlag, Matthew; Paulsen, Michelle; Sun, Lei; Shanley, Thomas P.; Ljungman, Mats; Nyati, Mukesh K.; Zhang, Ming; Lawrence, Theodore S. // PLoS ONE;Feb2013, Vol. 8 Issue 2, p1 

    The efficacy of radiation therapy for lung cancer is limited by radiation-induced lung toxicity (RILT). Although tumor necrosis factor-alpha (TNF-α) signaling plays a critical role in RILT, the molecular regulators of radiation-induced TNF-α production remain unknown. We investigated the...

  • CUX1 modulates polarization of tumor-associated macrophages by antagonizing NF-κB signaling. Kühnemuth, B; Mühlberg, L; Schipper, M; Griesmann, H; Neesse, A; Milosevic, N; Wissniowski, T; Buchholz, M; Gress, T M; Michl, P // Oncogene;1/8/2015, Vol. 34 Issue 2, p177 

    Many solid cancers including pancreatic ductal adenocarcinoma (PDAC) are characterized by an extensive stromal reaction that is accompanied by infiltrating tumor-associated macrophages (TAMs). The role of TAMs in malignant tumors is only partially understood. Previously, we identified the...

  • Role of Protein Tyrosine Phosphatase Non-Receptor Type 7 in the Regulation of TNF-α Production in RAW 264.7 Macrophages. Seo, Huiyun; Lee, In-Seon; Park, Jae Eun; Park, Sung Goo; Lee, Do Hee; Park, Byoung Chul; Cho, Sayeon // PLoS ONE;Nov2013, Vol. 8 Issue 11, p1 

    Protein tyrosine phosphatases play key roles in a diverse range of cellular processes such as differentiation, cell proliferation, apoptosis, immunological signaling, and cytoskeletal function. Protein tyrosine phosphatase non-receptor type 7 (PTPN7), a member of the phosphatase family,...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics