Inverse correlation between Leishmania-induced TLR1/2 and TGF-β differentially regulates parasite persistence in bone marrow during the chronic phase of infection.

Authors

Kamalika Roy, Sanhita Ghosh, Suman Karmakar, Pritam Mandal, Aabid Hussain, Aritri Dutta, Chiranjib Pal

Published in

Cytokine. Volume 185. Pages 156811. Epub Nov 28, 2024.

Abstract

Host-tissue preference is a critical aspect of parasitic infections and is directly correlated with species diversity. Even the same species, Leishmania donovani, infects the host's bone marrow, spleen, and liver differentially. The tissue-specific persistence of Leishmania results from host-pathogen immune conflicts and arguments. The protective pro-host or destructive pro-parasitic role of TLRs during L. donovani infection has been well established, but what entirely missing is the influence of TLRs on tissue-specific parasite persistence. We observed that the parasites induced differential expression of TLR1/2 in the bone marrow but not in the spleen. Interestingly, the rate of Leishmania infection was found to be positively correlated with TLR1/2-mediated upregulation of myelopoietic cytokines, M-CSF, GM-CSF, IL-6, and IL-3, leading to the expansion of Ly6C^hiCCR2⁺ monocytes, however, negatively correlated with the expression of the disease hallmark cytokines, TNF-α, TGF-β, and IL-10, along the course of infection in the bone marrow. Leishmania induced the activation of bone marrow-specific TLR1/2 to promote Ly6C^hiCCR2⁺ monocytes for its safe shelter vis-à-vis infection establishment. Consequently, the established infection initiated the release of TNF-α, TGF-β, and IL-10 in the bone marrow. Post-infection time-kinetic study affirmed that TGF-β had a significant negative influence on the expression of TLR1/2 heterodimer in the bone marrow niche. To the best of our knowledge, this is the first report to show that the inverse correlation of TLR1/2 - TGF-β can be instrumental in tissue-specific parasite persistence during Leishmania infection.

PMID:
39612658
Bibliographic data and abstract were imported from PubMed on 15 Apr 2025.

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