Mast cells are activated by Leishmania mexicana LPG and regulate the disease outcome depending on the genetic background of the host.
The regulatory effect of mast cells on the pathogenesis of leishmaniasis is unclear. We report a comparative analysis of TLR2 membrane expression, TNF-α, IL-10 and MIP-1α production, and granule release of bone marrow-derived mast cells (BMMCs) from susceptible BALB/c and resistant C57BL/6 mice, stimulated in vitro with Leishmania mexicana lipophosphoglycan (LPG). We studied the kinetics of mast cell degranulation and parasite numbers in lesions of both mouse strains infected with L. mexicana. We found that BMMCs of C57BL/6 mice expressed more TLR2 and produced higher levels of both cytokines and MIP-1α, whereas BALB/c BMMCs significantly augmented their granule release. Lesions of BALB/c mice showed higher levels of degranulated mast cells at 3 h of infection, whereas after 3 days of infection, the number of degranulated mast cells in C57BL/6 was higher than in BALB/c lesions. Throughout infection, BALB/c mice harboured more parasites. The regulatory effect of mast cells seems to depend on the genetic background of the host: mast cells of BALB/c mice facilitate disease progression due to an augmented inflammatory response early in the infection, whereas mast cells of C57BL/6 mice produce cytokines that regulate inflammation and maintain an elevated number of immune cells in the lesions, promoting disease control.
Villaseñor-Cardoso
M I
MI
Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., México.
Salaiza
N
N
Delgado
J
J
Gutiérrez-Kobeh
L
L
Pérez-Torres
A
A
Becker
I
I
D000818:Animals; D002452:Cell Count; D015550:Cell Degranulation; D054405:Chemokine CCL3 / Q000096:biosynthesis; D004195:Disease Models, Animal; D006028:Glycosphingolipids / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis; D007894:Leishmania mexicana / Q000276:immunology* / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012376:Rodent Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000469:parasitology / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D006028:Glycosphingolipids; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C008290:lipophosphonoglycan; D016753:Interleukin-10