Meta-tyrosine modulates the immune response induced by bacterial endotoxins

MONTAGNA DANIELA; ALEJANDRA DUARTE; TODERO MARÍA FLORENCIA; RUGGIERO RAÚL ; REARTE BÁRBARA ; ISTURIZ MARTIN

IMMUNOBIOLOGY.

ELSEVIER GMBH

Año: 2020

0171-2985

Sepsis is characterized by an early pro-inflammatory phase followed by compensatory anti-inflammatory mechanismsthat lead to a late generalized immunosuppression, period where most deaths occur. Immunotherapy approachesto recover the immunocompetence in sepsis are similar to those used in cancer. Meta-tyrosine (m-Tyr)is a product of oxidative stress present in circulation during the sepsis and cancer-associated pro-inflammatorystages. In this work,considering its potential participation in pro-inflammatory processes, we evaluate the effectof m-Tyr during LPS induced immunosuppression phase in a murine model. In addition, we examine the effectof m-Tyr in a vaccination strategy using a weakly immunogenic tumor model. Our results showed that m-Tyrcould prevent the establishment of immunosuppression and rescue the host from an installed immunosuppressioninduced by LPS. These effects were parallel to the ability of m-Tyr to improve the pro-inflammatory effectsinduced by LPS and inhibit the anti-inflammatory action of dexamethasone. Also, m-Tyr treatment prevents boththe reduction of splenic lymphocytes and the increase of the expression of programmed death ligand-1 in splenicmyeloid cellsassociated with immunosuppression. Besides, treatment with m-Tyr increased the protective effectof an anti-tumor vaccine, suggesting that m-Tyr could improve the immune response. In summary, we suggestthat m-Tyr can modulate critical immunological indicators through the inflammatory context, which could improvethe management of diseases, such as sepsis and cancer, in which immunosuppression is a significant clinicalproblem.