Anti-Tumor Necrosis Factor α Therapeutics Differentially Affect Leishmania Infection of Human Macrophages
Autor: | Peter Crauwels, Christodoulos Filippis, Helen Kleinfelder, Zoe Waibler, Katrin Bagola, Ger van Zandbergen, Katharina Arens, Gabriele Reichmann, Arthur Goetzee |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy T-Lymphocytes Immunology tumor necrosis factor α remicade® 03 medical and health sciences Humans Immunology and Allergy Medicine complement leishmaniasis Cells Cultured Original Research Leishmania human macrophages biology Tumor Necrosis Factor-alpha business.industry Effector T-cells Macrophages Adalimumab Antibodies Monoclonal biology.organism_classification Antibodies Neutralizing Coculture Techniques Infliximab Blockade Complement system Cytolysis 030104 developmental biology polyethylene glycol Certolizumab Pegol biology.protein PEGylation Tumor necrosis factor alpha cimzia® Antibody business lcsh:RC581-607 |
Zdroj: | Frontiers in Immunology, Vol 9 (2018) Frontiers in Immunology |
ISSN: | 1664-3224 |
Popis: | Tumor necrosis factor α (TNFα) drives the pathophysiology of human autoimmune diseases and consequently, neutralizing antibodies (Abs) or Ab-derived molecules directed against TNFα are essential therapeutics. As treatment with several TNFα blockers has been reported to entail a higher risk of infectious diseases such as leishmaniasis, we established an in vitro model based on Leishmania-infected human macrophages, co-cultured with autologous T-cells, for the analysis and comparison of anti-TNFα therapeutics. We demonstrate that neutralization of soluble TNFα (sTNFα) by the anti-TNFα Abs Humira®, Remicade®, and its biosimilar Remsima® negatively affects infection as treatment with these agents significantly reduces Leishmania-induced T-cell proliferation and increases the number of infected macrophages. By contrast, we show that blockade of sTNFα by Cimzia® does not affect T-cell proliferation and infection rates. Moreover, compared to Remicade®, treatment with Cimzia® does not impair the expression of cytolytic effector proteins in proliferating T-cells. Our data demonstrate that Cimzia® supports parasite control through its conjugated polyethylene glycol (PEG) moiety as PEGylation of Remicade® improves the clearance of intracellular Leishmania. This effect can be linked to complement activation, with levels of complement component C5a being increased upon treatment with Cimzia® or a PEGylated form of Remicade®. Taken together, we provide an in vitro model of human leishmaniasis that allows direct comparison of different anti-TNFα agents. Our results enhance the understanding of the efficacy and adverse effects of TNFα blockers and they contribute to evaluate anti-TNFα therapy for patients living in countries with a high prevalence of leishmaniasis. |
Databáze: | OpenAIRE |
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