Meta-tyrosine modulates the immune response induced by bacterial endotoxins

DANIELA ROMINA MONTAGNA; ALEJANDRA DUARTE; MARÍA FLORENCIA TODERO; RAÚL ALEJANDRO RUGGIERO; MARTÍN ISTURIZ; BÁRBARA REARTE

IMMUNOBIOLOGY.

ELSEVIER GMBH

Año: 2020

0171-2985

Sepsis is characterized by an early pro-inflammatory phase followed by compensatory anti-inflammatory mechanisms that lead to a late generalized immunosuppression, period in which the majority of deaths from sepsis occur. Immunotherapy approaches to recover the immunocompetence in sepsis are widely shared with those used in cancer. Meta-tyrosine (m-Tyr) is a product of oxidative stress present in circulation during the sepsis and cancer-associated pro-inflammatory stages. Considering its potential participation in pro-inflammatory processes, in this work we evaluate the effect of m-Tyr during LPS induced immunosuppression phase in a murine model. In addition, we examine the effect of m-Tyr in a vaccination strategy using a weakly immunogenic tumor model. Our results showed that m-Tyr could prevent the establishment of immunosuppression and rescue the host from an installed immunosuppression induced by LPS. These effects were parallel to the ability of m-Tyr to improve the pro-inflammatory effects induced by LPS and inhibit the anti-inflammatory action of dexamethasone. Also, m-Tyr treatment prevents both the reduction splenic lymphocytes and the increase in the expression of programmed death ligand-1 in splenic myeloid cells, events associated to the immunosuppression. Besides, treatment with m-Tyr increased the protective effect of vaccination directed against a tumor, suggesting an improvement in the antitumor response. In summary, we suggest that m-Tyr can modulate critical immunological indicators through the inflammatory context, which could improve the management of diseases, such as sepsis and cancer, in which immunosuppression is a significant clinical problem.