Effect of Brucella spp. Lumazine Synthase in regulatory T cells and its impact on antitumoral immunity.

FARIAS, ANA; ROSSI, ANDRÉS HUGO; BEROL, L.; GOLDBAUM, FERNANDO A.; SPARWASSER, T.; BERGUER, PAULA M.

Mar del Plata

Congreso; LXIV Reunión científica anual de la sociedad Argentina de inmunología SAI; 2016

SAI

Melanoma patients harbor increased numbers of Foxp3(+)regulatory T cells (Treg), impeding the onset of antitumoral response.Treg depletion has been adopted as a promising therapeuticapproach however the precise mechanism and receptorsinvolved remains unclear. Brucella spp. lumazine synthase (BLS)is a decameric protein with highly immunogenic properties. Wehave previously demonstrated that BLS induces a protective antitumoralresponse in mice with B16 melanoma. We inoculated micesc with BLS and 20 or 35 days later induced tumor developmentby sc injecting B16 cells. Treatment significantly inhibited tumorgrowth and 50% of mice failed to develop a tumor. Furthermore,the protective effect by BLS was abolished in TLR4 deficient micesuggesting the importance in signaling through this receptor. Ina first attempt to decipher the mechanism involved, we analyzedthe effect of BLS in Treg generation from naïve T cells in vitrounder Treg differentiation conditions. BLS decreased the percen tageof Foxp3+ Treg, with a marked reduction in the expressionof FoxP3. Moreover, the effect of BLS was partially abolished inMyD88-/- mice suggesting that signaling through alternate receptorsmay be involved. We next evaluated the effect of BLS in Treg invivo. Our results showed that after 20 days post BLS treatmentthere is a higher number of CD4+ cells and CD4+Foxp3+ cells inthe draining lymph node. However, after 35 days only recruitmentof CD4+FoxP3- cells was observed.Thus decrease in Tregs in thetumor microenvironment by FoxP3 downregulation may explainhowBLS mechanistically regulates antitumoral responses.