Resposta eritropoiética envolvida na suscetibilidade de camundongos infantes à malária

• Ano de defesa: 2022
• Autor(a) principal: Camila Dutra Moreira de Miranda
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS; Programa de Pós-Graduação em Biologia Celular; UFMG
• Palavras-chave em Português: Malária; Eritropoiese; Fígado; Célula de Kupffer; Suscetibilidade; Infante; Biologia Celular; Eritropoese; Macrófagos do Fígado; Suscetibilidade a Doenças
• Link de acesso: http://hdl.handle.net/1843/44457

Malaria remains a major threat to public health worldwide, and children under 5 years old are the main fatal victims of this disease. The liver plays an essential role in the course of infection. The singular characteristics of the hepatic endothelium, together with different immune cell populations, including tissue macrophages, are directly involved in serious complications, such as severe malarial anemia, responsible for a large number of infant deaths. Studies developed by our group show that the liver undergoes a hematopoietic transition throughout postnatal development, and the spleen and bone marrow of neonates have different cell profiles when compared to adults. However, studies on the relationship between hematopoietic development and the severity of malaria and experimental models that reproduce childhood susceptibility are lacking. Aim: To propose an experimental model in mice that can be useful in understanding the mortality of children from malaria, characterizing the dynamics and mechanisms involved in erythropoiesis in response to Plasmodium chabaudi infection. Results and conclusion: We standardized malaria infection in mice in different ages throughout life, and a higher parasitemia in infant mice than in neonates and adults was observed. In addition, infant mice infected with P. chabaudi presented anemia at the peak of infection and did not survive. Using flow cytometry, we saw that the hematopoietic niches of infants - bone marrow, spleen and liver - showed increased erythroid precursors during malarial infection, whereas adults suppress erythropoiesis. We also showed that there is a greater number of erythrocyte precursors in the peripheral blood of infant animals than in adults, and these precursors can be infected by P. chabaudi, contributing to the group's hyperparasitemia and consequent lethality.