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Regulatory role of Transcription factor-EB (TFEB) in parasite control through alteration of antigen presentation in visceral leishmaniasis.
Ghosh, Rishila; Jawed, Junaid Jibran; Roy, Nivedita; Mandal, Supriya; Majumdar, Suchandra Bhattacharya; Majumdar, Subrata.
Afiliação
  • Ghosh R; Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII- M, Kolkata, 700 054, West Bengal, India.
  • Jawed JJ; Institute of Health Sciences, Presidency University (2nd Campus), Plot No. DG/02/02, Premises No. 14-0358, Action Area 1D (Newtown), Kolkata, 700156, West Bengal, India.
  • Roy N; Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII- M, Kolkata, 700 054, West Bengal, India.
  • Mandal S; Institute of Health Sciences, Presidency University (2nd Campus), Plot No. DG/02/02, Premises No. 14-0358, Action Area 1D (Newtown), Kolkata, 700156, West Bengal, India.
  • Majumdar SB; Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII- M, Kolkata, 700 054, West Bengal, India.
  • Majumdar S; Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII- M, Kolkata, 700 054, West Bengal, India. Electronic address: subrata@jcbose.ac.in.
Exp Parasitol ; 239: 108286, 2022 Aug.
Article em En | MEDLINE | ID: mdl-35660529
ABSTRACT
Leishmania donovani, an obligate intracellular parasite, the causative agent of visceral leishmaniasis is known to subvert the host immune system for its own survival. Although the precise mechanism is still unknown, emerging evidences indicate that L. donovani efficiently suppress MHC I mediated antigen presentation, rendering inadequate CD8+T cell activation and weakening host defense against parasite. The role of transcription factor EB (TFEB) was recognized in modulating antigen presentation besides its role in lysosomal biogenesis and function. Here, we investigated the regulatory role of TFEB in the modulation of presentation of Leishmania antigen in host tissue. Our results showed an increased expression of TFEB after Leishmania infection both in vitro and in vivo and there was a decrease in the expression of Th-1 cytokine IFNγ along with MHC class I and CD8+T cells indicating attenuation of cell mediated immunity and possibly MHC I restricted antigen presentation. Silencing of TFEB resulted in increased expression of IFNγ and MHC I along with increased CD8+T cells population without any significant change in CD4+T cell number. We also observed a decreased parasite burden in TFEB silenced condition which indicates enhanced parasite clearance by alteration of immunological response possibly through induction of presentation of Leishmania antigen through MHC I. The present study explains the role of TFEB silencing in parasite clearance through regulating the antigen presentation of Leishmania antigen thereby promises to formulate a potential therapeutic strategy against visceral leishmaniasis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leishmania donovani / Leishmaniose Visceral Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leishmania donovani / Leishmaniose Visceral Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article