TNF-BLOCKADE IN B CELL-DEFICIENT MICE INFECTED WITH TRYPANOSOMA CRUZI EXACERBATES A SYSTEMIC INFLAMMATORY RESPONSE AND INCREASES SUSCEPTIBILITY TO INFECTION

GOROSITO SERRÁN M; BERMEJO DA; TOSELLO BOARI J; RAMELLO MC; AMEZCUA VESELY MC; MONTES CL; ACOSTA RODRIGUEZ EV; GRUPPI A

Congreso; First Argentinean Spring Course in Advance Immunology and LXI Reunión Anual de la Sociedad Argentina de Inmunología.; 2013

B cell-deficient mice (C129.BL6uMT) (uMT) infected with T. cruzi Y-br strain were more susceptible to the infection than control C57BL/6 mice (WT) as 70 % of infected uMT died after day 22 post-infection (d22pi), while 100% of WT control survived. Considering that 30% of uMT infected mice survived to the infection, we classified uMT infected mice in susceptible (who died before d22pi) and resistant (who survived as WT). We found that serum TNF in susceptible uMT was higher than WT?s, whereas in resistant uMT TNF concentration was similar to WT?s. In order to evaluate the role of TNF in uMT infected mice, uMT intraperitoneally infected with 10000 trypomastigotes were injected, since d13pi, with anti TNF-specific Rat IgG1 (TuMT) (1.5 mg/week) or with control Rat IgG (CuMT). Anti-TNF treated mice recovered the 100% of their weight lost after starting treatment, but surprisingly had a dramatic loss before dying, while CuMT lost a 20% of their weight and kept only their 80% (WT=100% d0-30pi). We observed that TuMT mice presented increased mortality (60% of TuMT and 100% of CuMT and WT mice survived by d30pi). TuMT mice had higher concentrations of serum TNF, IFNg, and IL12 (determined by quantitative ELISA) than CuMT and WT mice on d21 and d28pi (p