학술논문
Vitamin A deficiency impairs neutrophil-mediated control of Salmonella via SLC11A1 in mice
Document Type
Original Paper
Author
Lokken-Toyli, Kristen L.; Diaz-Ochoa, Vladimir E.; Camacho, Lizbeth; Stull-Lane, Annica R.; Van Hecke, Amber E. R.; Mooney, Jason P.; Muñoz, Ariel D.; Walker, Gregory T.; Hampel, Daniela; Jiang, Xiaowen; Labuda, Jasmine C.; Depew, Claire E.; McSorley, Stephen J.; Stephensen, Charles B.; Tsolis, Renée M.
Source
Nature Microbiology. 9(3):727-736
Subject
Language
English
ISSN
2058-5276
Abstract
In sub-Saharan Africa, multidrug-resistant non-typhoidal Salmonella serovars are a common cause of fatal bloodstream infection. Malnutrition is a predisposing factor, but the underlying mechanisms are unknown. Here we show that vitamin A deficiency, one of the most prevalent micronutrient deficits afflicting African children, increases susceptibility to disseminated non-typhoidal Salmonella disease in mice and impairs terminal neutrophil maturation. Immature neutrophils had reduced expression of Slc11a1, a gene that encodes a metal ion transporter generally thought to restrict pathogen growth in macrophages. Adoptive transfer of SLC11A1-proficient neutrophils, but not SLC11A1-deficient neutrophils, reduced systemic Salmonella burden in Slc11a1−/− mice or mice with vitamin A deficiency. Loss of terminal granulopoiesis regulator CCAAT/enhancer-binding protein ϵ (C/EBPϵ) also decreased neutrophil-mediated control of Salmonella, but not that mediated by peritoneal macrophages. Susceptibility to infection increased in Cebpe−/− Slc11a1+/+ mice compared with wild-type controls, in an Slc11a1-expression-dependent manner. These data suggest that SLC11A1 deficiency impairs Salmonella control in part by blunting neutrophil-mediated defence.
Vitamin A deficiency exacerbates invasive non-typhoidal Salmonella infection in mice, revealing a restrictive role for SLC11A1 in neutrophils.
Vitamin A deficiency exacerbates invasive non-typhoidal Salmonella infection in mice, revealing a restrictive role for SLC11A1 in neutrophils.