1,25-Dihydroxyvitamin D3 induces splenocyte apoptosis and enhances BALB/c mice sensitivity to toxoplasmosis.
The hormonal form of Vitamin D, 1,25-dihydroxyvitamin D3, is well known for its immunosuppressive, anti-proliferative and pro-apoptotic activities. In the present work, we studied the effect of 1,25-dihydroxyvitamin D3 on Toxoplasma gondii-infected mice. We observed that 1,25-dihydroxyvitamin D3 reduces the survival rate of infected mice by up to 37% at day 10 post-infection compared to untreated infected mice (P < 0.0001). IFN-gamma and IL-12p40 levels were significantly reduced by 1,25-dihydroxyvitamin D3 in infected mice sera indicating an inhibition of Th-1-type cytokines. CD4+ T lymphocyte and splenocyte counts were also reduced following 1,25-dihydroxyvitamin D3 treatment and a marked induction of apoptosis, accompanied with down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-X(L), was observed. The above results indicate that 1,25-dihydroxyvitamin D3 induces splenocyte apoptosis and enhances host susceptibility to toxoplasmosis.
Rajapakse
Rohan
R
Institut National de la Santé Et de la Recherche Médicale UMR-S 392, Institut de Parasitologie et de Pathologie Tropicale, Faculté de Médicine, 3 rue de Koeberlé, 67000 Strasbourg, France.
Mousli
Marc
M
Pfaff
Alexander W
AW
Uring-Lambert
Béatrice
B
Marcellin
Luc
L
Bronner
Christian
C
Jeanblanc
Michaël
M
Villard
Odile
O
Letscher-Bru
Valérie
V
Klein
Jean-Paul
JP
Candolfi
Ermanno
E
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004198:Disease Susceptibility; D007113:Immunity, Innate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D015996:Survival Rate; D014123:Toxoplasmosis / Q000401:mortality / Q000503:physiopathology*
D007166:Immunosuppressive Agents; D002117:Calcitriol