Monocyte cytokine and costimulatory molecule expression in patients infected with Leishmania mexicana.
Leishmania mexicana causes localized and diffuse cutaneous leishmaniasis. Patients with localized cutaneous leishmaniasis (LCL) develop a benign disease, whereas patients with diffuse cutaneous leishmaniasis (DCL) suffer from a progressive disease associated with anergy of the cellular response towards Leishmania antigens. We evaluated the production of the interleukins (IL) IL-12, IL-15, IL-18 and tumour necrosis factor-alpha (TNF-alpha) and the expression of the costimulatory molecules CD40, B7-1 and B7-2 in monocytes from LCL and DCL patients, stimulated in vitro with Leishmania mexicana lipophosphoglycan (LPG) for 18 h. LCL monocytes significantly increased TNF-alpha, IL-15 and IL-18 production, and this increase was associated with reduced amounts of IL-12. DCL monocytes produced no IL-15 or IL-18 and showed a decreasing tendency of TNF-alpha and IL-12 production as the severity of the disease increased. No difference was observed in the expression of CD40 and B7-1 between both groups of patients, yet B7-2 expression was significantly augmented in DCL patients. It remains to be established if this elevated B7-2 expression in DCL patients is cause or consequence of the Th2-type immune response that characterizes these patients. These data suggest that the diminished ability of the monocytes from DCL patients to produce cell-activating innate proinflammatory cytokines when stimulated with LPG is a possible cause for disease progression.
Carrada
G
G
Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., México.
Cañeda
C
C
Salaiza
N
N
Delgado
J
J
Ruiz
A
A
Sanchez
B
B
Gutiérrez-Kobeh
L
L
Aguirre
M
M
Becker
I
I
D000293:Adolescent; D000328:Adult; D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006028:Glycosphingolipids / Q000008:administration & dosage; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D019409:Interleukin-15 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D016774:Leishmaniasis, Diffuse Cutaneous / Q000276:immunology*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D006028:Glycosphingolipids; D019409:Interleukin-15; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; C008290:lipophosphonoglycan; D018664:Interleukin-12