Combined immunotherapeutic effect of Leishmania-derived recombinant aldolase and Ambisome against experimental visceral leishmaniasis
Background: Available therapeutics for visceral leishmaniasis (VL), a deadly parasitic infection, are usually associated with inadequate efficacy and adverse aftereffects. Further, the primary site of Leishmania parasite are host macrophages resulting in compromised immunity; ensuing marked T-cell i...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Journal of Microbiology, Immunology and Infection |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1684118222000949 |
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| author | Keerti Narendra Kumar Yadav Sumit Joshi Sneha Ratnapriya Amogh Anant Sahasrabuddhe Anuradha Dube |
| author_facet | Keerti Narendra Kumar Yadav Sumit Joshi Sneha Ratnapriya Amogh Anant Sahasrabuddhe Anuradha Dube |
| author_sort | Keerti |
| collection | DOAJ |
| description | Background: Available therapeutics for visceral leishmaniasis (VL), a deadly parasitic infection, are usually associated with inadequate efficacy and adverse aftereffects. Further, the primary site of Leishmania parasite are host macrophages resulting in compromised immunity; ensuing marked T-cell immunosuppression. Such settings emphasize the exploration of chemo-immunotherapeutic strategies for improvising the infected person’s immune status with better resolution of infection. Methods: Present work employs the immunization of Leishmania-infected hamsters with Leishmania-derived recombinant aldolase (rLdAld) and enolase (rLdEno) proteins in consort with the sub-optimal dose of Ambisome (2.5 mg/kg). After the completion of immunization, hamsters were sacrificed on day 60 and 90 post infection and different organ samples were collected to perform immunological assay for evaluating the therapeutic efficacy and modulation in protective cellular immune responses. Results: Combining these proteins, particularly rLdAld with Ambisome (2.5 mg/kg), has significantly reduced the parasitic load (∼80%) with remarkable enhancement in DTH and lymphoproliferative responses compared to the infected control and only Ambisome treated groups. Moreover, cytokine levels at RNA and protein levels were noticed to be inclined towards Th-1 phenotype through up-regulation of IFN-γ and TNF-α with significant down-regulation in IL-10 and TGF-β expression, an indication towards the generation of protective immunity against experimental VL. Conclusion: Our experimental findings demonstrated that the chemo-immunotherapeutic approach could be an effective way of controlling human VL infection at minimal dosages of antileishmanial with reduced side-effects and propensity of drug resistance emergence. |
| first_indexed | 2024-04-10T18:30:25Z |
| format | Article |
| id | doaj.art-ec850d1504724b70bad26fcb303715e0 |
| institution | Directory Open Access Journal |
| issn | 1684-1182 |
| language | English |
| last_indexed | 2024-04-10T18:30:25Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Microbiology, Immunology and Infection |
| spelling | doaj.art-ec850d1504724b70bad26fcb303715e02023-02-02T04:47:38ZengElsevierJournal of Microbiology, Immunology and Infection1684-11822023-02-01561163171Combined immunotherapeutic effect of Leishmania-derived recombinant aldolase and Ambisome against experimental visceral leishmaniasis Keerti0Narendra Kumar Yadav1Sumit Joshi2Sneha Ratnapriya3Amogh Anant Sahasrabuddhe4Anuradha Dube5Divisions of Molecular and Structural Biology, CSIR-CDRI, Lucknow 226031, IndiaDivisions of Molecular and Structural Biology, CSIR-CDRI, Lucknow 226031, IndiaParasitology, CSIR-CD-RI, Lucknow 226031, IndiaDivisions of Molecular and Structural Biology, CSIR-CDRI, Lucknow 226031, IndiaDivisions of Molecular and Structural Biology, CSIR-CDRI, Lucknow 226031, India; Corresponding author.Parasitology, CSIR-CD-RI, Lucknow 226031, India; Corresponding author.Background: Available therapeutics for visceral leishmaniasis (VL), a deadly parasitic infection, are usually associated with inadequate efficacy and adverse aftereffects. Further, the primary site of Leishmania parasite are host macrophages resulting in compromised immunity; ensuing marked T-cell immunosuppression. Such settings emphasize the exploration of chemo-immunotherapeutic strategies for improvising the infected person’s immune status with better resolution of infection. Methods: Present work employs the immunization of Leishmania-infected hamsters with Leishmania-derived recombinant aldolase (rLdAld) and enolase (rLdEno) proteins in consort with the sub-optimal dose of Ambisome (2.5 mg/kg). After the completion of immunization, hamsters were sacrificed on day 60 and 90 post infection and different organ samples were collected to perform immunological assay for evaluating the therapeutic efficacy and modulation in protective cellular immune responses. Results: Combining these proteins, particularly rLdAld with Ambisome (2.5 mg/kg), has significantly reduced the parasitic load (∼80%) with remarkable enhancement in DTH and lymphoproliferative responses compared to the infected control and only Ambisome treated groups. Moreover, cytokine levels at RNA and protein levels were noticed to be inclined towards Th-1 phenotype through up-regulation of IFN-γ and TNF-α with significant down-regulation in IL-10 and TGF-β expression, an indication towards the generation of protective immunity against experimental VL. Conclusion: Our experimental findings demonstrated that the chemo-immunotherapeutic approach could be an effective way of controlling human VL infection at minimal dosages of antileishmanial with reduced side-effects and propensity of drug resistance emergence.http://www.sciencedirect.com/science/article/pii/S1684118222000949AmbisomeChemo-immunotherapyHamsterLeishmania donovani and Recombinant aldolase (rLdAld) |
| spellingShingle | Keerti Narendra Kumar Yadav Sumit Joshi Sneha Ratnapriya Amogh Anant Sahasrabuddhe Anuradha Dube Combined immunotherapeutic effect of Leishmania-derived recombinant aldolase and Ambisome against experimental visceral leishmaniasis Journal of Microbiology, Immunology and Infection Ambisome Chemo-immunotherapy Hamster Leishmania donovani and Recombinant aldolase (rLdAld) |
| title | Combined immunotherapeutic effect of Leishmania-derived recombinant aldolase and Ambisome against experimental visceral leishmaniasis |
| title_full | Combined immunotherapeutic effect of Leishmania-derived recombinant aldolase and Ambisome against experimental visceral leishmaniasis |
| title_fullStr | Combined immunotherapeutic effect of Leishmania-derived recombinant aldolase and Ambisome against experimental visceral leishmaniasis |
| title_full_unstemmed | Combined immunotherapeutic effect of Leishmania-derived recombinant aldolase and Ambisome against experimental visceral leishmaniasis |
| title_short | Combined immunotherapeutic effect of Leishmania-derived recombinant aldolase and Ambisome against experimental visceral leishmaniasis |
| title_sort | combined immunotherapeutic effect of leishmania derived recombinant aldolase and ambisome against experimental visceral leishmaniasis |
| topic | Ambisome Chemo-immunotherapy Hamster Leishmania donovani and Recombinant aldolase (rLdAld) |
| url | http://www.sciencedirect.com/science/article/pii/S1684118222000949 |
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