Combination of Mycobacterium indicus pranii and Heat-Induced Promastigotes Cures Drug-Resistant Leishmania Infection: Critical Role of Interleukin-6-Producing Classical Dendritic Cells.

Authors

Somaditya Dey, Debarati Mukherjee, Sirin Salma Sultana, Suvadip Mallick, Aritri Dutta, Joydip Ghosh, Aabid Hussain, Biswajyoti Sarkar, Supratim Mandal, Pradyumna Patra, Bhaskar Saha, Chiranjib Pal

Published in

Infection and immunity. Volume 88. Issue 6. May 20, 2020. Epub May 20, 2020.

Abstract

The major issues in available therapeutic modalities against leishmaniasis are cost, toxicity, and the emergence of drug resistance. The aim of this work was to develop a successful therapeutic adjuvant against drug-resistant Leishmania donovani infection by means of combining Mycobacterium indicus pranii with heat-induced promastigotes (HIP). One-month postinfected BALB/c mice were administered subcutaneously with M. indicus pranii (10⁸ cells) and HIP (100 μg) for 5 days. Spleens were harvested for flow cytometric and reverse transcriptase PCR analysis. The antileishmanial effect of the combination strategy was associated with induction of a disease-resolving Th1 and Th17 response with simultaneous downregulation of CD4⁺ CD25⁺ Foxp3⁺ (nTreg) cells and CD4⁺ CD25^- Foxp3^- (Tr1) cells in the spleen. The significant expansion of CD4⁺ T_CM (CD4⁺ CD44^hi CD11a^hi CD62L^hi) cells was a further interesting outcome of this therapeutic strategy in the context of long-term protection of hosts against secondary infection. Toll-like receptor 2 (TLR2) was also found instrumental in this antiparasitic therapy. Induced interleukin-6 (IL-6) production from expanded CD11c⁺ CD8α⁺ (cDC1) and CD11c⁺ CD11b⁺ (cDC2) dendritic cells (DCs) but not from the CD11b⁺ Ly6c⁺ inflammatory monocytes (iMOs), was found critical in the protective expansion of Th17 as evidenced by an in vivo IL-6 neutralization assay. It also promoted the hematopoietic conversion toward DC progenitors (pre-DCs) from common dendritic cell progenitors (CDPs), the immediate precursors, in bone marrow. This novel combinational strategy demonstrated that expansion of Th17 by IL-6 released from CD11c⁺ classical DCs is crucial, together with the conventional Th1 response, to control drug-resistant infection.

PMID:
32229617
Bibliographic data and abstract were imported from PubMed on 15 Apr 2025.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.