IL-1α protects intestinal barrier in murine visceral leishmaniasis
5 affiliations
- 1Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- 2Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- 3Academic Institute of Health and Biological Sciences, Goiás State University, Itumbiara, Brazil
- 4Fiocruz-Bi-Institutional Translational Medicine Project, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
- 5Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
Abstract
Interleukin-1 (IL-1) is a pleiotropic cytokine important in inflammatory and infectious diseases, but its roles in visceral leishmaniasis (VL) remain poorly understood. Here, we evaluated the role of IL-1 cytokines during experimental visceral leishmaniasis. We showed that IL-1 receptor 1 (IL-1R1) deficiency enhanced the gamma interferon (IFNγ)-mediated response and restricted parasites in an IL-1α-dependent manner, whereas IL-1β deficiency had no effect. The absence of IL-1R1 and IL-1α led to intestinal microbiota dysbiosis. The infection induced IL-1α expression in the gut. The absence of IL-1α led to reduced expression of tight-junction molecules, increased intestinal permeability, and bacterial translocation. These alterations amplified non-Leishmania-specific IFN-γ production, which was reversed by broad-spectrum antibiotic treatment. Bone marrow chimeric transplantation showed that hematopoietic cells are the source of IL-1α during VL. Together, our findings reveal that IL-1α acts as a key regulator of gut barrier integrity in VL and indirectly restrains systemic IFNγ-driven inflammation. This work highlights IL-1α-dependent intestinal protection as an overlooked component of VL pathogenesis.
IMPORTANCE: Visceral leishmaniasis (VL) is a systemic and chronic disease caused by Leishmania parasites. Most infected individuals remain asymptomatic due to an appropriate IFNγ-mediated response. By contrast, the disease progression is characterized by excessive inflammation, with high levels of cytokines, among them IFNγ. IL-1 cytokines play a role in modulating immune responses and epithelial barriers. We report that IL-1α protects the intestinal environment and indirectly regulates the IFNγ-mediated response during experimental VL. The infection induces IL-1α expression in the intestine, and its absence leads to dysbiosis, gut permeability, and bacterial translocation. Overall, this study reveals the role of IL-1α in intestinal integrity during VL and in regulating the IFNγ-mediated response. Expanding the knowledge of IL-1α in intestinal protection may support therapeutic approaches to improve the outcomes of infection.
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BibTeX
@article{sacramento2026il1α,
title = {{IL-1α protects intestinal barrier in murine visceral leishmaniasis}},
author = {Laís A. Sacramento and Pedro Alexandre Sampaio and Gabriela Castilho Martins and Luciana Benevides and Claudia Gonzalez-Lombana and Gabrielle B. Trindade and Michely Mello and Fernando Q. Cunha and Livia S. Zaramela and João S. Silva and Phillip Scott and Vanessa Carregaro},
journal = {mBio},
year = {2026},
month = sep,
doi = {10.1128/mbio.00657-26},
url = {https://doi.org/10.1128/mbio.00657-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - IL-1α protects intestinal barrier in murine visceral leishmaniasis
AU - Laís A. Sacramento
AU - Pedro Alexandre Sampaio
AU - Gabriela Castilho Martins
AU - Luciana Benevides
AU - Claudia Gonzalez-Lombana
AU - Gabrielle B. Trindade
AU - Michely Mello
AU - Fernando Q. Cunha
AU - Livia S. Zaramela
AU - João S. Silva
AU - Phillip Scott
AU - Vanessa Carregaro
PY - 2026
DA - 2026/09/14
JO - mBio
DO - 10.1128/mbio.00657-26
UR - https://doi.org/10.1128/mbio.00657-26
AB - Interleukin-1 (IL-1) is a pleiotropic cytokine important in inflammatory and infectious diseases, but its roles in visceral leishmaniasis (VL) remain poorly understood. Here, we evaluated the role of IL-1 cytokines during experimental visceral leishmaniasis. We showed that IL-1 receptor 1 (IL-1R1) deficiency enhanced the gamma interferon (IFNγ)-mediated response and restricted parasites in an IL-1α-dependent manner, whereas IL-1β deficiency had no effect. The absence of IL-1R1 and IL-1α led to intestinal microbiota dysbiosis. The infection induced IL-1α expression in the gut. The absence of IL-1α led to reduced expression of tight-junction molecules, increased intestinal permeability, and bacterial translocation. These alterations amplified non-Leishmania-specific IFN-γ production, which was reversed by broad-spectrum antibiotic treatment. Bone marrow chimeric transplantation showed that hematopoietic cells are the source of IL-1α during VL. Together, our findings reveal that IL-1α acts as a key regulator of gut barrier integrity in VL and indirectly restrains systemic IFNγ-driven inflammation. This work highlights IL-1α-dependent intestinal protection as an overlooked component of VL pathogenesis. IMPORTANCE: Visceral leishmaniasis (VL) is a systemic and chronic disease caused by Leishmania parasites. Most infected individuals remain asymptomatic due to an appropriate IFNγ-mediated response. By contrast, the disease progression is characterized by excessive inflammation, with high levels of cytokines, among them IFNγ. IL-1 cytokines play a role in modulating immune responses and epithelial barriers. We report that IL-1α protects the intestinal environment and indirectly regulates the IFNγ-mediated response during experimental VL. The infection induces IL-1α expression in the intestine, and its absence leads to dysbiosis, gut permeability, and bacterial translocation. Overall, this study reveals the role of IL-1α in intestinal integrity during VL and in regulating the IFNγ-mediated response. Expanding the knowledge of IL-1α in intestinal protection may support therapeutic approaches to improve the outcomes of infection.
SN - 2150-7511
ER -