Banca de DEFESA: REGINALDO BRITO DOS SANTOS JUNIOR

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : REGINALDO BRITO DOS SANTOS JUNIOR
DATE: 24/05/2022
TIME: 13:00
LOCAL: IGM Sala Virtual 3
TITLE:

B cell differentiation and plasmacytosis in the course of splenic disorganization in visceral leishmaniasis: an experimental study in hamsters

KEY WORDS:

Plasma cells; Gene expression; DLK1; Immunohistochemistry

PAGES: 110
BIG AREA: Ciências Biológicas
AREA: Imunologia
SUMMARY:

ABSTRACT
Introduction: Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania infantum, which internal organs are compromised. In the spleen the infection is chronic and progressive. In addition, in severe VL, there is disruption of splenic compartments, a decrease of B cells number in the white pulp (WP) and plasmacytosis in the red pulp (RP). Plasma cells have extended survival and accumulated in many chronic diseases. However, poorly is known about the functions and mechanisms of generation and maintenance of cell survival. Objective: In this work, we investigated the potential mechanisms associated with the abnormal development of B cells that lead to plasmacytosis during VL. Methods: 56 Golden Syrian hamsters with 6 to 8 weeks were used in this study: 28 were injected intraperitoneally with 1x107 L. infantum promastigotes and 28 received the diluent solution by the same route. Seven animals from each group were euthanized 30-, 60-, 120- and 150-days post-injection (dpi). The animals were necropsied and organ samples were fixed in paraffin for histological study and evaluation of B cell and plasma cell distribution by immunohistochemistry. For three animals from each group and at each point, a spleen fragment was collected for transcriptomic evaluation of gene expression and association between molecules related to B cell development, including a molecule called DLK1. Results: There was an increase in the WP of the infected animals at 120 dpi, while at the 150 dpi there was atrophy affecting the follicle, which might be related to a decrease in B cells. We also observed a reduction in B cell chemotaxis, due to the decrease in CXCL13 and CXCL12 that occurred at 120 and 150 dpi. We noticed a toward to decrease molecular factors related to the germinal center (GC) response, observed by the gene expression of infected hamsters. There were no changes in the amount of B cells in the RP of the infected animals, but there was progressive plasmacytosis in the RP of the animals at the later stages of the disease, 120 and 150 dpi and the accumulation of these cells in the T cell zone at 120 dpi, DLK1 was associated with the plasmacytosis in RP. The gene expression of infected animals confirmed the differentiation of plasma cells at 150 dpi and associated signaling by IL-21 and IFN-γ such the main molecules involved. In addition, there was an increase in IL-6 150 dpi. Conclusions: In this study we correlated structural and cellular changes with molecular expression to investigate the determinants of B cell anomaly in severe forms of VL. There were increased of IL-21 and IFN-γ related with the B cell differentiation and plasma cell generation to latter disease stages. In addition, we demonstrated a decrease in CXCL13, CXCL12 and increase in IL-6. Moreover, there was an increase in the proportion of B cells at 120 dpi but decrease at 150 dpi in WP and plasmacytosis in RP.

BANKING MEMBERS:
Externo à Instituição - WAGNER LUIZ TAFURI - UFMG
Interna - 233.804.895-49 - CLAUDIA IDA BRODSKYN - UFBA
Presidente - 1205225 - WASHINGTON LUIS CONRADO DOS SANTOS