Galectin-3 plays a modulatory role in the life span and activation of murine neutrophils during early Toxoplasma gondii infection.
Galectins are beta-galactoside-binding lectins involved in several biological processes and galectin-3 (Gal-3) is related to modulation of immune and inflammatory responses. This study aimed to evaluate the role of Gal-3 in the life span and biological functions of murine neutrophils during in vitro infection by virulent Toxoplasma gondii RH strain. Inflammatory peritoneal neutrophils (Nphi) from C57BL/6 wild-type (WT) and Gal-3 knockout (KO) mice were cultured in the presence or absence of parasites and analyzed for phosphatidylserine (PS) exposure and cell death using Annexin-V and propidium iodide staining, and cell viability by MTT assay. Cell toxicities determined by lactate dehydrogenase (LDH), degranulation by lysozyme release, and cytokine production were measured in Nphi culture supernatants. Phorbol myristate acetate (PMA)- or zymosan-dependent reactive oxygen species (ROS) were measured in Nphi cultures. Our results demonstrated that Gal-3 is involved in the increase of the viable Nphi number and the decrease of PS exposure and cell death following T. gondii infection. We also observed that Gal-3 downmodulates T. gondii-induced Nphi toxicity as well as Nphi degranulation regardless of infection. Furthermore, Gal-3 expression by Nphi was associated with increased levels of IL-10 in the beginning and decreased levels of TNF-alpha later on, regardless of parasite infection, as well as with decreased levels of IL-6 and increased IL-12 levels, following early parasite infection. Our results also showed that Gal-3 suppresses PMA- but not zymosan-induced ROS generation in Nphi following T. gondii infection. In conclusion, Gal-3 plays an important modulatory role by interfering in Nphi life span and activation during early T. gondii infection.
Alves
Celene M O S
CM
Laboratory of Immunoparasitology, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, Brazil.
Silva
Deise A O
DA
Azzolini
Ana Elisa C S
AE
Marzocchi-Machado
Cleni M
CM
Carvalho
Julianne V
JV
Pajuaba
Ana Cláudia A M
AC
Lucisano-Valim
Yara Maria
YM
Chammas
Roger
R
Liu
Fu-Tong
FT
Roque-Barreira
Maria C
MC
Mineo
José R
JR
D000818:Animals; D015550:Cell Degranulation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D037502:Galectin 3 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018375:Neutrophil Activation / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology* / Q000378:metabolism; D014123:Toxoplasmosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D037502:Galectin 3; C485095:Lgals3 protein, mouse; D017382:Reactive Oxygen Species