ORIGINAL RESEARCH article
Front. Immunol.
Sec. Parasite Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1634080
Protein dysregulation during Leishmania infantum infection in anti-TNF immunosuppressed mice revealed through quantitative proteomics analysis of extracellular vesicles
Provisionally accepted
Lorena Bernardo1,2*
Ana Montero Calle3
Jose Carlos Solana1,2*
Marina Lozano-Rendal1
Ana Torres1
Carmen Sánchez1
Rodrigo Barderas3,4
Javier Moreno1,2
Eugenia Carrillo1,2- 1WHO Collaborating Centre for Leishmaniasis, National Center for Microbiology, Majadahonda, Spain
- 2Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- 3Chronic Disease Program (UFIEC), Instituto de Salud Carlos III, Majadahonda, Spain
- 4Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain
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Introduction: Visceral leishmaniasis (VL) occurs more frequently in immunosuppressed individuals, especially those undergoing immunosuppressive drug therapy for an autoimmune disease. In those receiving TNF antagonist therapy (anti-TNF), the course of VL is more severe and the response to traditional leishmanicidal treatments, such as antimonials (Sb), is often reduced. This effect of anti-TNF treatment is observed in our immunosuppressed-mouse model of VL. In this model, we compared anti-TNF immunosuppression with no immunosuppression before and after VL treatment with Sb.Methods: Serum-derived extracellular vesicles (EVs) were analyzed through label-free quantitative proteomics to identify proteins involved in both VL severity and the impact of anti-TNF immunosuppression on treatment outcome. Results: In total, 223 dysregulated proteins were found in the pre-treatment groups, the majority of which, such as vitronectin, haemopexin or caveolin-1, were downregulated in the anti-TNF samples. In contrast, 173 proteins were identified in the Sb-treatment groups, most of which were found enriched in the anti-TNF plus treatment samples (anti-TNF+Sb) including fibronectin, transferrin, vitronectin and dipeptidyl peptidase-4. These differentially-expressed proteins were associated with pathways related to the immune system, liver regeneration, and ion transport. Conclusion: Our findings have useful implications for the clinical management of VL patients under anti-TNF immunosuppression.
Keywords: extracellular vesicles, Visceral leishmaniasis, Immunosuppression, TNF antagonist, Antimonials, Quantitative Proteomics, LFQ proteomics analyses, biomarkers
Received: 23 May 2025; Accepted: 14 Jul 2025.
Copyright: © 2025 Bernardo, Montero Calle, Solana, Lozano-Rendal, Torres, Sánchez, Barderas, Moreno and Carrillo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lorena Bernardo, WHO Collaborating Centre for Leishmaniasis, National Center for Microbiology, Majadahonda, Spain
Jose Carlos Solana, WHO Collaborating Centre for Leishmaniasis, National Center for Microbiology, Majadahonda, Spain
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