Influ?ncia de linf?citos B-1 na din?mica de leuc?citos de animais deficientes da Tirosina Quinase de Bruton (XID)

• Autor(a) principal: Correia, Carolina de Albuquerque
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFRRJ
• Texto Completo: https://tede.ufrrj.br/jspui/handle/jspui/6358
• topic: Linf?citos B-1; Inflama??o; Modula??o; B-1 lymphocytes; Inflammation; Modulation; Medicina Veterin?ria

Inflammation is a physiological reaction of the body to an offending agent and can be triggered by infection and/or injury. The acute phase of this process is a rapid response and occurs in the first minutes and hours after pathogen recognition. Its resolution usually results in the elimination of infectious agents and repair of the normal tissue architecture and function. The chronic phase begins when attempts to restore homeostasis are unsuccessful. Often, the action of phagocytes is sufficient to contain inflammation, however, if the harmful stimulus lasts, other agents of the immune system are activated, configuring the inflammation within the adaptive response. Dendritic cells make the connection between the innate and adaptive immune responses, as they are specialized in processing and exposing fragments of antigens to T lymphocytes. These, in turn, assist in the activation of B-lymphocytes, which are cells capable of producing and secrete antibodies and form memory cells. B-1 lymphocytes are a subpopulation of B-lymphocytes, characterized by the production of natural antibodies, presentation of antigens to T lymphocytes and the release of various cytokines, including the anti-inflammatory cytokine IL-10. Thus, they have the potential to modulate the inflammatory response. In this work, we evaluated the population dynamics of leukocytes in the blood and in the peritoneal cavity of BALB/c and XID mice during the acute inflammatory response, triggered by LPS. Thus, we used XID mice, whose peritoneum is an environment with very few B-1 lymphocytes. Our results revealed that XID animals spontaneously have a high number of neutrophils in peripheral blood and this population is even greater after stimulation with LPS. Concomitantly, high levels of IL-6 were detected. In addition, the peritoneal cavity of these animals also has a greater amount of neutrophils, compared to BALB/c mice. This data does not change after stimulation in our experimental conditions. In phagocyte assays, we found out that the number of macrophages capable of phagocyting is statistically equal between BALB/c and XID, but the number of internalized yeasts is lower in the XID LPS+IFN-? group. This suggests an increased microbicidal activity of the macrophages of these mice. This result is corroborated by the dosage of nitrite in the culture supernatant, in which the stimulated XID macrophages produced more nitric oxide than the control group. Our results together suggest an ability to develop a more intense inflammatory response in XID mice compared to BALB/c mice, probably due to the impairment in the production of the anti-inflammatory cytokine IL-10. Therefore, our analysis reports for the first time that XID mice have an increased number of neutrophil populations in the blood and peritoneal cavity when compared to BALB/c, indicating the importance of B-1 lymphocytes in modulating the inflammatory response and suggesting that these may be future targets of investigations in immunotherapy strategies