Leishmania donovani mitogen-activated protein kinases as a host-parasite interaction interface.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9005353 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0023 (Electronic) Linking ISSN: 10434666 NLM ISO Abbreviation: Cytokine Subsets: MEDLINE
    • Publication Information:
      Publication: <2001- > : Oxford : Elsevier Science Ltd.
      Original Publication: [Philadelphia, PA] : Saunders Scientific Publications, W.B. Saunders, [c1989-
    • Subject Terms:
      Leishmania donovani*/enzymology ; Host-Parasite Interactions* ; Mitogen-Activated Protein Kinases*/metabolism ; Macrophages*/parasitology ; Macrophages*/metabolism; Animals ; Mice ; Humans ; Mice, Inbred BALB C ; Phosphorylcholine/analogs & derivatives ; Phosphorylcholine/pharmacology ; Leishmaniasis, Visceral/parasitology ; Leishmaniasis, Visceral/immunology ; Protozoan Proteins/metabolism ; Protozoan Proteins/genetics ; Interferon-gamma/metabolism ; Drug Resistance
    • Abstract:
      Leishmaniasis, a major globally re-emerging neglected tropical disease, has a restricted repertoire of chemotherapeutic options due to a narrow therapeutic index, drug resistance, or patient non-compliance due to toxicity. The disease is caused by the parasite Leishmania that resides in two different forms in two different environments: as sessile intracellular amastigotes within mammalian macrophages and as motile promastigotes in sandfly gut. As mitogen-activated protein kinases (MAPKs) play important roles in cellular differentiation and survival, we studied the expression of Leishmania donovani MAPKs (LdMAPKs). The homology studies by multiple sequence alignment show that excepting LdMAPK1 and LdMAPK2, all thirteen other LdMAPKs share homology with human ERK and p38 isoforms. Expression of LdMAPK4 and LdMAPK5 is less in avirulent promastigotes and amastigotes. Compared to miltefosine-sensitive L. donovani parasites, miltefosine-resistant parasites have higher LdMAPK1, LdMAPK3-5, LdMAPK7-11, LdMAPK13, and LdMAPK14 expression. IL-4-treatment of macrophages down-regulated LdMAPK11, in virulent amastigotes whereas up-regulated LdMAPK5, but down-regulated LdMAPK6, LdMAPK12-15, expression in avirulent amastigotes. IL-4 up-regulated LdMAPK1 expression in both virulent and avirulent amastigotes. IFN-γ-treatment down-regulated LdMAPK6, LdMAPK13, and LdMAPK15 in avirulent amastigotes but up-regulated in virulent amastigotes. This complex profile of LdMAPKs expression among virulent and avirulent parasites, drug-resistant parasites, and in amastigotes within IL-4 or IFN-γ-treated macrophages suggests that LdMAPKs are differentially controlled at the host-parasite interface regulating parasite survival and differentiation, and in the course of IL-4 or IFN-γ dominated immune response.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier Ltd. All rights reserved.)
    • Contributed Indexing:
      Keywords: Drug-resistance; Host-pathogen interaction; Immune response; Leishmania MAPK; Leishmaniasis; Virulence factor
    • Accession Number:
      0 (miltefosine)
    • Publication Date:
      Date Created: 20240504 Date Completed: 20240519 Latest Revision: 20240605
    • Publication Date:
      20240605
    • Accession Number:
      10.1016/j.cyto.2024.156627
    • Accession Number:
      38703436