Data_Sheet_1_Anti-Tumor Necrosis Factor α Therapeutics Differentially Affect Leishmania Infection of Human Macrophages.PDF Katharina Arens Christodoulos Filippis Helen Kleinfelder Arthur Goetzee Gabriele Reichmann Peter Crauwels Zoe Waibler Katrin Bagola Ger van Zandbergen 10.3389/fimmu.2018.01772.s001 https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_Anti-Tumor_Necrosis_Factor_Therapeutics_Differentially_Affect_Leishmania_Infection_of_Human_Macrophages_PDF/6880643 <p>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<sup>®</sup>, Remicade<sup>®</sup>, and its biosimilar Remsima<sup>®</sup> 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<sup>®</sup> does not affect T-cell proliferation and infection rates. Moreover, compared to Remicade<sup>®</sup>, treatment with Cimzia<sup>®</sup> does not impair the expression of cytolytic effector proteins in proliferating T-cells. Our data demonstrate that Cimzia<sup>®</sup> supports parasite control through its conjugated polyethylene glycol (PEG) moiety as PEGylation of Remicade<sup>®</sup> 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<sup>®</sup> or a PEGylated form of Remicade<sup>®</sup>. 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.</p> 2018-07-31 06:35:52 tumor necrosis factor α remicade® cimzia® polyethylene glycol leishmaniasis complement human macrophages T-cells