Arginase as a marker of disease severity in human leishmaniasis

1
Arginase as a marker of disease severity in human
leishmaniasis Addis Ababa University, Ethiopia
Imperial College London, UK
L-arginine
L-arginine
L-arginine
T cells
L-arginine
L-arginine
L-arginine
L-arginine
Macrophages
L-arginine
L-arginine
L-arginine
L-arginine
T cells
L-arginine
arginase
L-arginine
T cells
L-arginine
L-arginine
L-arginine
T cells
L-arginine
T cells
T cells
T cells
L-arginine
arginase
L-arginine
T cells
T cells proliferate and produce cytokines
gt poor T cell activation
T cells
T cells
L-arginine
In patients suffering from non-healing
leishmaniasis, T cells have an impaired capacity
to produce Interferon gamma.
L-arginine
Arginase-induced L-arginine depletion results in
T cell hyporesponsiveness
T cells unconditionally require L-arginine to
become efficient effector cells
Infected macrophages

• 16 localised cutaneous leishmaniasis patients

arginase
Addis Ababa
L-arginine

• 11 diffuse cutaneous leishmaniasis patients

L-arginine
Addis Ababa University Black Lion Hospital
T cells

• 10 controls

Specimens 1 x 3 mm skin biopsy
High arginase low L-arginine gt poor T
cell activation
Biopsies
80
70
60
50
Addis Ababa University Black Lion Hospital
40
Arginase activity (mU/mg protein)
30
20
10
N.D.
0
Control
LCL
DCL
controls

• Recruit more cutaneous leishmaniasis patients
• Recruit visceral leishmaniasis patients (Gondar
  and Arba Minch)
• Measure the levels of - Arginase
• - L-arginine

Localised cutaneous leishmaniasis
Diffused cutaneous leishmaniasis
Control
Results
High arginase is expressed in the biopsies, i.e.
at the site of pathology