Analysis of germinal centers in mice with Chagas’ disease treated with NIPOx-B

Abstract

Abstract Chagas’ disease is caused by the parasite Trypanosome cruzi; it affects 10 million people in Latin America and it remains incurable: the only drugs available for its treatment, Benznidazole (Bz) and Nifurtimox (Nx), are inefficient to cure patients. The chronic phase of the disease is characterized by megacolon and megaesophagus; this phase is established by parasite evasion of the host adaptive immunity, a process that is facilitated by the free radicals generated by Bz and Nx, which affect lymphocytes and other immune cells. We designed and synthesized the benzyl ester of N-isopropyl oxamic acid (NIPOx-B) and determined that it is an effective inhibitor of alpha-hydroxy acid dehydrogenase II enzyme, a key enzyme in the parasite metabolism. NIPOx-B is more efficient than Bz and Nx in decreasing mice parasitemia. In this work, we studied by flow cytometry the cell populations in germinal centers in mice with Chagas’ disease, untreated or treated with Bz or with NIPOx-B. The percentage and the activation of B cells, macrophages, CD4 lymphocytes, dendritic and follicular dendritic cells in germinal centers were higher in mice treated with NIPOx-B than in mice treated with Bz. The IgG and IgE antibodies titers were also higher in mice treated with NIPOx-B. Untreated mice had the lowest cell percentages and antibody titers. Mice treated with NIPOx-B did not develop megasyndromes, while untreated mice or mice treated with Bz developed them. Because NIPOx-B has trypanomicidal activity and did not affect the percentage of cells involved in the immune response it can be proposed as a drug for the treatment of Chagas’ disease.