Bernardo, LorenaSolana, Jose CarlosSanchez Herrero, CarmenTorres Garcia, Ana MariaReyes-Cruz, Eder YavethCarrillo, EugeniaMoreno, Javier2024-01-122024-01-122023Front Immunol. 2023 Dec 1:14:1285943.http://hdl.handle.net/20.500.12105/16952Background: Immunosuppression is a major risk factor for the development of visceral leishmaniasis (VL). The number of patients receiving immunosuppressant drugs such as TNF antagonist (anti-TNF) and methotrexate (MTX) is increasing. In these patients, VL is more severe, their response to treatment poorer, and they are at higher risk of relapse, a consequence (largely) of the poor and inappropriate immune response they develop. Objectives: To examine the effect of immunosuppressive treatment on the host immune response and thus gain insight into the reduced efficacy of pentavalent antimonials in these patients. Experiments were performed using BALB/c mice immunosuppressed with anti-TNF or MTX, infected with Leishmania infantum promastigotes, and then treated with Glucantime® at clinical doses. Results: Immunosuppression with both agents impeded parasite elimination from the spleen and bone marrow. Low pro-inflammatory cytokine production by CD4+ and CD8+ T cells was detected, along with an increase in PD-1 and IL-10 expression by B and T cells in the immunosuppressed groups after treatment. Conclusion: The immunosuppressed mice were unable to develop specific cellular immunity to the parasite, perhaps explaining the greater risk of VL relapse seen in pharmacologically immunosuppressed human patients.engVoRhttp://creativecommons.org/licenses/by/4.0/Visceral leishmaniasisImmunosuppressionImmunosuppressantsBALB/c miceTNF antagonistMethotrexateGlucantime®Leishmania infantumLeishmaniasisLeishmaniasis, VisceralParasitesHumansAnimalsMiceMeglumine AntimoniateCD8-Positive T-LymphocytesImmunosuppressive AgentsTumor Necrosis Factor InhibitorsDisease Models, AnimalImmunity, CellularRecurrenceAtribución 4.0 Internacional14128594310.3389/fimmu.2023.12859431664-3224Frontiers in immunologyopen access