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LXR Deficiency Confers Increased Protection against Visceral Leishmania Infection in Mice
Journal article   Open access

LXR Deficiency Confers Increased Protection against Visceral Leishmania Infection in Mice

Kevin W Bruhn, Chaitra Marathe, Ana Cláudia Maretti-Mira, Hong Nguyen, Jacquelyn Haskell, Thu Anh Tran, Veena Vanchinathan, Upasna Gaur, Mary E Wilson, Peter Tontonoz, …
PLoS neglected tropical diseases, Vol.4(11), pp.e886-e886
11/2010
DOI: 10.1371/journal.pntd.0000886
PMCID: PMC2982826
PMID: 21103366
url
https://doi.org/10.1371/journal.pntd.0000886View
Published (Version of record) Open Access

Abstract

Leishmania spp. are protozoan single-cell parasites that are transmitted to humans by the bite of an infected sand fly, and can cause a wide spectrum of disease, ranging from self-healing skin lesions to potentially fatal systemic infections. Certain species of Leishmania that cause visceral (systemic) disease are a source of significant mortality worldwide. Here, we use a mouse model of visceral Leishmania infection to investigate the effect of a host gene called LXR. The LXRs have demonstrated important functions in both cholesterol regulation and inflammation. These processes, in turn, are closely related to lipid metabolism and the development of atherosclerosis. LXRs have also previously been shown to be involved in protection against other intracellular pathogens that infect macrophages, including certain bacteria. We demonstrate here that LXR is involved in susceptibility to Leishmania , as animals deficient in the LXR gene are much more resistant to infection with the parasite. We also demonstrate that macrophages lacking LXR kill parasites more readily, and make higher levels of nitric oxide (an antimicrobial mediator) and IL-1β (an inflammatory cytokine) in response to Leishmania infection. These results could have important implications in designing therapeutics against this deadly pathogen, as well as other intracellular microbial pathogens.
Immunology Infectious Diseases Medical Microbiology Microbiology Parasitology Immunity to Infections Protozoal Infections Cellular Microbiology and Pathogenesis Innate Immunity Neglected Tropical Diseases

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