IFN-λ3 is induced by Leishmania donovani and can inhibit parasite growth in cell line models but not in the mouse model, while it shows a significant association with leishmaniasis in humans.

Autor:	De M; National Institute of Biomedical Genomics, Kalyani, West Bengal, India., Sukla S; National Institute of Pharmaceutical Education and Research, Kolkata, West Bengal, India.; Centre for High Impact Neuroscience and Translational Applications (CHINTA), TCG-Centres for Research and Education in Science and Technology, Kolkata, West Bengal, India., Bharatiya S; National Institute of Biomedical Genomics, Kalyani, West Bengal, India.; Regional Centre for Biotechnology, Faridabad, India., Keshri S; National Institute of Biomedical Genomics, Kalyani, West Bengal, India.; Regional Centre for Biotechnology, Faridabad, India., Roy DG; National Institute of Biomedical Genomics, Kalyani, West Bengal, India.; Regional Centre for Biotechnology, Faridabad, India., Roy S; Department of Pharmacology, Institute of Post-Graduate Medical Education and Research, Kolkata, India., Dutta D; National Institute of Pharmaceutical Education and Research, Kolkata, West Bengal, India., Saha S; National Institute of Biomedical Genomics, Kalyani, West Bengal, India., Ejazi SA; Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.; Fischell Department of Bioengineering, A. James Clark School of Engineering, University of Maryland, College Park, MD, USA., Ravichandiran V; National Institute of Pharmaceutical Education and Research, Kolkata, West Bengal, India., Ali N; Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India., Chatterjee M; Department of Pharmacology, Institute of Post-Graduate Medical Education and Research, Kolkata, India., Chinnaswamy S; National Institute of Biomedical Genomics, Kalyani, West Bengal, India.; Regional Centre for Biotechnology, Faridabad, India.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2024 Feb 13; Vol. 92 (2), pp. e0050423. Date of Electronic Publication: 2024 Jan 09.
DOI:	10.1128/iai.00504-23
Abstrakt:	The intracellular protozoan parasite Leishmania donovani causes debilitating human diseases that involve visceral and dermal manifestations. Type 3 interferons (IFNs), also referred to as lambda IFNs (IFNL, IFN-L, or IFN-λ), are known to play protective roles against intracellular pathogens at the epithelial surfaces. Herein, we show that L. donovani induces IFN-λ3 in human as well as mouse cell line-derived macrophages. Interestingly, IFN-λ3 treatment significantly decreased parasite load in infected cells , mainly by increasing reactive oxygen species production. Microscopic examination showed that IFN-λ3 inhibited uptake but not replication, while the phagocytic ability of the cells was not affected. This was confirmed by experiments that showed that IFN-λ3 could decrease parasite load only when added to the medium at earlier time points, either during or soon after parasite uptake, but had no effect on parasite load when added at 24 h post-infection, suggesting that an early event during parasite uptake was targeted. Furthermore, the parasites could overcome the inhibitory effect of IFN-λ3, which was added at earlier time points, within 2-3 days post-infection. BALB/c mice treated with IFN-λ3 before infection led to a significant increase in expression of IL-4 and ARG1 post-infection in the spleen and liver, respectively, and to different pathological changes, especially in the liver, but not to changes in parasite load. Treatment with IFN-λ3 during infection did not decrease the parasite load in the spleen either. However, IFN-λ3 was significantly increased in the sera of visceral leishmaniasis patients, and the IFNL genetic variant rs12979860 was significantly associated with susceptibility to leishmaniasis. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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