Cathepsin G and neutrophil elastase control Leishmania infantum parasitism through TLRs-dependent induction of IFN-α and TNF-α
- 1Laboratory of Biochemisty and Molecular Biology of Proteases, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro
- 2Laboratory of Molecular Parasitology, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro
- 3York Biomedical Research Institute and Department of Biology, University of York
Abstract
Leishmania infantum and Leishmania donovani are protozoan parasites that cause visceral leishmaniasis, a potentially fatal disease targeting the liver, spleen and bone marrow. To survive, these parasites manipulate host macrophage microbicidal responses and metabolic pathways. Here, we demonstrate that the host serine proteases neutrophil elastase (NE) and cathepsin G (CG), acting in concert with Toll-like receptors TLR2, TLR3, and TLR4, induce the inflammatory cytokines IFN-α and TNF-α to control L. infantum infection in macrophages. Conversely, in vivo experiments revealed that while NE and CG are necessary for inflammatory responses, including IL-12, nitric oxide, and CCL2 production, they unexpectedly promote splenic parasitism. CG-deficient mice failed to recruit Ly6Chi myeloid cells to the spleen, providing a potential mechanism for their reduced parasite burden. Finally, our data suggest that unlike L. donovani, L. infantum cannot hijack cellular host serine peptidases and TLR signalling for survival, yet it remains dependent on these host enzymes to establish systemic spleen infection.
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BibTeX
@article{goundry2026cathepsin,
title = {{Cathepsin G and neutrophil elastase control Leishmania infantum parasitism through TLRs-dependent induction of IFN-α and TNF-α}},
author = {Amy Goundry and Aislan C. Vivarini and Nathalia S. Rodrigues and Ulisses G. Lopes and Jeremy C. Mottram and Ana Paula C. A. Lima},
journal = {Communications Biology},
year = {2026},
month = jun,
doi = {10.1038/s42003-026-10555-8},
url = {https://doi.org/10.1038/s42003-026-10555-8},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cathepsin G and neutrophil elastase control Leishmania infantum parasitism through TLRs-dependent induction of IFN-α and TNF-α
AU - Amy Goundry
AU - Aislan C. Vivarini
AU - Nathalia S. Rodrigues
AU - Ulisses G. Lopes
AU - Jeremy C. Mottram
AU - Ana Paula C. A. Lima
PY - 2026
DA - 2026/06/01
JO - Communications Biology
DO - 10.1038/s42003-026-10555-8
UR - https://doi.org/10.1038/s42003-026-10555-8
AB - Leishmania infantum and Leishmania donovani are protozoan parasites that cause visceral leishmaniasis, a potentially fatal disease targeting the liver, spleen and bone marrow. To survive, these parasites manipulate host macrophage microbicidal responses and metabolic pathways. Here, we demonstrate that the host serine proteases neutrophil elastase (NE) and cathepsin G (CG), acting in concert with Toll-like receptors TLR2, TLR3, and TLR4, induce the inflammatory cytokines IFN-α and TNF-α to control L. infantum infection in macrophages. Conversely, in vivo experiments revealed that while NE and CG are necessary for inflammatory responses, including IL-12, nitric oxide, and CCL2 production, they unexpectedly promote splenic parasitism. CG-deficient mice failed to recruit Ly6Chi myeloid cells to the spleen, providing a potential mechanism for their reduced parasite burden. Finally, our data suggest that unlike L. donovani, L. infantum cannot hijack cellular host serine peptidases and TLR signalling for survival, yet it remains dependent on these host enzymes to establish systemic spleen infection.
SN - 2399-3642
ER -