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Metabolic, immune, and gut microbial signals mount a systems response to Leishmania major infection

Lamour, Sabrina D., Veselkov, Kirill A., Posma, Joram M., Giraud, Emilie, Rogers, Matthew E., Croft, Simon, Marchesi, Julian Roberto, Holmes, Elaine, Seifert, Karin and Saric, Jasmina 2015. Metabolic, immune, and gut microbial signals mount a systems response to Leishmania major infection. Journal of Proteome Research 14 (1) , pp. 318-329. 10.1021/pr5008202

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Parasitic infections such as leishmaniasis induce a cascade of host physiological responses, including metabolic and immunological changes. Infection with Leishmania major parasites causes cutaneous leishmaniasis in humans, a neglected tropical disease that is difficult to manage. To understand the determinants of pathology, we studied L. major infection in two mouse models: the self-healing C57BL/6 strain and the nonhealing BALB/c strain. Metabolic profiling of urine, plasma, and feces via proton NMR spectroscopy was performed to discover parasite-specific imprints on global host metabolism. Plasma cytokine status and fecal microbiome were also characterized as additional metrics of the host response to infection. Results demonstrated differences in glucose and lipid metabolism, distinctive immunological phenotypes, and shifts in microbial composition between the two models. We present a novel approach to integrate such metrics using correlation network analyses, whereby self-healing mice demonstrated an orchestrated interaction between the biological measures shortly after infection. In contrast, the response observed in nonhealing mice was delayed and fragmented. Our study suggests that trans-system communication across host metabolism, the innate immune system, and gut microbiome is key for a successful host response to L. major and provides a new concept, potentially translatable to other diseases.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology
Uncontrolled Keywords: host; response; infection; metabolic; profiling; microbiota; cytokine; multivariate; correlation; Leishmania
Publisher: American Chemical Society
ISSN: 1535-3893
Date of First Compliant Deposit: 30 March 2016
Last Modified: 02 Jul 2019 05:20

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