Proteolytic activity of secreted proteases from pathogenic leptospires and effects on phagocytosis by murine macrophages
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2023
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Immunobiology
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Leptospirosis is a zoonosis caused by spirochete bacteria that
belong to the genus Leptospira. This disease represents a serious
public health problem, especially in developing countries with
tropical and subtropical temperatures. Pathogenic leptospires
escape from the Complement System, a property that permits
them to survive in vitro when in contact with normal human
serum (NHS). In a previous study carried out by our group, it was
observed that culture supernatants from different pathogenic species
of leptospires (SPL) contain proteases that cleave many Complement
proteins, including the central molecule C3 and its
fragments C3b and iC3b. Our hypothesis is that these proteases,
could decrease the phagocytic clearance of leptospires. Using flow
cytometry, we observed decreased amounts of CR3 and CR4 in
murine peritoneal macrophages treated with SPL for 24 h. By confocal
microscopy, we observed reduction in TLR2, CD11b and
CD206 levels when these cells were treated with SPL and recombinant
thermolysin for 24 h. Furthermore, opsonins such as C3b/iC3b
deposited on the surface of pathogenic leptospires were observed
to be completely degraded in the presence of SPL or recombinant
thermolysin. Finally, we decided to investigate the phagocytosis
of pathogenic leptospires by macrophages in the presence of these
proteases. We observed an increase of phagocytosis of leptospires
opsonized with normal mouse serum even when macrophages
were treated with the proteases. However, when opsonized bacteria
were also incubated with SPL, recombinant thermolysin and
recombinant leptolysin., there was a decline in leptospires phagocytosis.
This suggests that the proteolytic activity can affect phagocytosis
by peritoneal macrophages mainly through the degradation
of opsonins deposited in the membrane of leptospires. These
observations lead us to suggest that proteases secreted by pathogenic
leptospires could degrade opsonins present in normal serum
or deposited in the bacterial membrane as well as cleave or inhibit
macrophage surface molecules. Therefore, these proteases could
interfere with the recognition and internalization by murine
macrophages, favoring the spread of leptospires in the host.
Como referenciar
AMAMURA, THAIS; COURROL, DANIELLA; BARBOSA, ANGELA; SILVA JÚNIOR, ILDEFONSO; SILVA, TIAGO da; MIDON, LEONARDO; HEINEMANN, MARCOS B.; CHAMBI, ROSA C.; MORGANTI, LIGIA; ISAAC, LOURDES. Proteolytic activity of secreted proteases from pathogenic leptospires and effects on phagocytosis by murine macrophages. Immunobiology, v. 228, n. 5, p. 45, 2023. DOI: 10.1016/j.imbio.2023.152562. Disponível em: http://repositorio.ipen.br/handle/123456789/34407. Acesso em: 08 Sep 2024.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.