Protein energy malnutrition increases arginase activity in monocytes and macrophages.
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.
Department of Medicine, Section of Immunology, Faculty of Medicine, Imperial College London, Norfolk Place, London, W2 1PG UK.
Karina
K
Corware
Immunology and Infection Department, London School of Hygiene and Tropical Medicine, London, UK.
Vanessa
V
Yardley
Department of Medicine, Section of Immunology, Faculty of Medicine, Imperial College London, Norfolk Place, London, W2 1PG UK.
Christopher
C
Mack
Department of Biochemistry, WHO Immunology Research and Training Center, University of Lausanne, Lausanne, Switzerland.
Steffen
S
Schuster
Department of Medicine, Section of Immunology, Faculty of Medicine, Imperial College London, Norfolk Place, London, W2 1PG UK.
Hafid
H
Al-Hassi
School of Biological Sciences, Royal Holloway, University of London, Egham, UK.
Shanthi
S
Herath
International AIDS Vaccine Initiative Human Immunology Laboratory, Faculty of Medicine, Imperial College London, London, UK.
Philip
P
Bergin
Department of Cellular Immunology, Max-Planck-Institute for Immunobiology and Epigenetics, Freiburg, Germany.
Manuel
M
Modolell
Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center Mainz, Mainz, Germany.
Markus
M
Munder
Department of Medicine, Section of Immunology, Faculty of Medicine, Imperial College London, Norfolk Place, London, W2 1PG UK.
Ingrid
I
Müller
Department of Medicine, Section of Immunology, Faculty of Medicine, Imperial College London, Norfolk Place, London, W2 1PG UK.
Pascale
P
Kropf
Arginase; Leishmaniasis; Macrophages; Monocytes; Nitric oxide