Protein energy malnutrition increases arginase activity in monocytes and macrophages

Nutrition & Metabolism

Pascale Kropf⁶  Ingrid Müller⁶  Markus Munder⁴  Manuel Modolell⁵  Philip Bergin²  Shanthi Herath¹  Hafid Al-Hassi⁶  Steffen Schuster⁷  Christopher Mack⁶  Vanessa Yardley³  Karina Corware⁶ 

[1] School of Biological Sciences, Royal Holloway, University of London, Egham, UK;International AIDS Vaccine Initiative Human Immunology Laboratory, Faculty of Medicine, Imperial College London, London, UK;Immunology and Infection Department, London School of Hygiene and Tropical Medicine, London, UK;Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center Mainz, Mainz, Germany;Department of Cellular Immunology, Max-Planck-Institute for Immunobiology and Epigenetics, Freiburg, Germany;Department of Medicine, Section of Immunology, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK;Department of Biochemistry, WHO Immunology Research and Training Center, University of Lausanne, Lausanne, Switzerland

关键词: Leishmaniasis;    Nitric oxide;    Monocytes;    Macrophages;    Arginase;   

Others  :  1130862
DOI  :  10.1186/1743-7075-11-51

 received in 2014-05-20, accepted in 2014-09-24,  发布年份 2014

【 摘 要 】

Background

Protein energy malnutrition is commonly associated with immune dysfunctions and is a major factor in susceptibility to infectious diseases.

Methods

In this study, we evaluated the impact of protein energy malnutrition on the capacity of monocytes and macrophages to upregulate arginase, an enzyme associated with immunosuppression and increased pathogen replication.

Results

Our results show that monocytes and macrophages are significantly increased in the bone marrow and blood of mice fed on a protein low diet. No alteration in the capacity of bone marrow derived macrophages isolated from malnourished mice to phagocytose particles, to produce the microbicidal molecule nitric oxide and to kill intracellular Leishmania parasites was detected. However, macrophages and monocytes from malnourished mice express significantly more arginase both in vitro and in vivo. Using an experimental model of visceral leishmaniasis, we show that following protein energy malnutrition, the increased parasite burden measured in the spleen of these mice coincided with increased arginase activity and that macrophages provide a more permissive environment for parasite growth.

Conclusions

Taken together, these results identify a novel mechanism in protein energy malnutrition that might contributes to increased susceptibility to infectious diseases by upregulating arginase activity in myeloid cells.

【 授权许可】

   
2014 Corware et al.; licensee BioMed Central Ltd.

【 图 表 】

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