Toxoplasma gondii infection reveals a novel regulatory role for galectin-3 in the interface of innate and adaptive immunity.
In attempts to investigate the role of galectin-3 in innate immunity, we studied galectin-3-deficient (gal3-/-) mice with regard to their response to Toxoplasma gondii infection, which is characterized by inflammation in affected organs, Th-1-polarized immune response, and accumulation of cysts in the central nervous system. In wild-type (gal3+/+) mice, infected orally, galectin-3 was highly expressed in the leukocytes infiltrating the intestines, liver, lungs, and brain. Compared with gal3+/+, infected gal3-/- mice developed reduced inflammatory response in all of these organs but the lungs. Brain of gal3-/- mice displayed a significantly reduced number of infiltrating monocytes/macrophages and CD8+ cells and a higher parasite burden. Furthermore, gal3-/- mice mounted a higher Th1-polarized response and had comparable survival rates on peroral T. gondii infection, even though they were more susceptible to intraperitoneal infection. Interestingly, splenic cells and purified CD11c+ dendritic cells from gal3-/- mice produced higher amounts of interleukin-12 than cells from gal3+/+ mice, possibly explaining the higher Th1 response verified in the gal3-/- mice. We conclude that galectin-3 exerts an important role in innate immunity, including not only a pro-inflammatory effect but also a regulatory role on dendritic cells, capable of interfering in the adaptive immune response.
Bernardes
Emerson Soares
ES
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto-USP, Av. dos Bandeirantes, 3900, Ribeirão Preto-SP, Brazil-CEP 14049-900.
Silva
Neide M
NM
Ruas
Luciana Pereira
LP
Mineo
Jose Roberto
JR
Loyola
Adriano Motta
AM
Hsu
Daniel K
DK
Liu
Fu-Tong
FT
Chammas
Roger
R
Roque-Barreira
Maria Cristina
MC
D000818:Animals; D039521:CD11c Antigen / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology; D037502:Galectin 3 / Q000378:metabolism / Q000502:physiology*; D007107:Immune System; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology; D014122:Toxoplasma / Q000378:metabolism*; D014123:Toxoplasmosis / Q000378:metabolism*; D014124:Toxoplasmosis, Animal / Q000378:metabolism*; D015854:Up-Regulation
D039521:CD11c Antigen; D037502:Galectin 3; D018664:Interleukin-12