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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Leptospira interrogans Lsa23 protein recruits plasminogen, factor H and C4BP from normal human serum and mediates C3b and C4b degradation

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Autor(es):
Siqueira, Gabriela H. [1, 2] ; Atzingen, Marina V. [3] ; de Souza, Gisele O. [4] ; Vasconcellos, Silvio A. [4] ; Nascimento, Ana L. T. O. [1, 2]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Inst Butantan, Ctr Biotecnol, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Inst Ciencias Biomed, Ave Prof Lineu Prestes 1730, BR-05508900 Sao Paulo - Brazil
[3] Adolfo Lutz Inst, Ave Doutor Arnaldo 355, BR-01246000 Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Fac Med Vet & Zootecnia, Lab Zoonoses Bacterianas VPS, Ave Prof Dr Orlando Marques de Paiva 87, BR-05508270 Sao Paulo, SP - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: MICROBIOLOGY-SGM; v. 162, n. 2, p. 295-308, FEB 2016.
Citações Web of Science: 13
Resumo

It has been reported that pathogenic Leptospira are resistant to normal human serum (NHS) due to their ability to evade the complement immune system by interacting with factor H (FH) and C4b-binding protein (C4BP) regulators. Moreover, plasmin generation on the leptospiral surface diminishes C3b and IgG deposition, decreasing opsonophagocytosis by immune competent cells. We have previously reported that Lsa23 (LIC11360) is a multipurpose protein capable of binding purified extracellular matrix molecules, FH, C4BP and plasminogen (PLG)/plasmin in the presence of PLG activators. In this work, we provide further evidence that Lsa23 is located at the bacterial surface by using immunofluorescence microscopy. We show that Lsa23 has the ability to acquire FH, C4BP and PLG from NHS, and use these interactions to evade innate immunity. The binding with the complement regulators FH and C4BP preserves factor I (FI) activity, leading to C3b and C4b degradation products, respectively. C3b and C4b alpha-chain cleavage was also observed when Lsa23 bound to PLG generating plasmin, an effect blocked by the protease inhibitor aprotinin. Lsa23 also inhibited lytic activity by NHS mediated by both classical and alternative complement pathways. Thus, Lsa23 has the ability to block both pathways of the complement system, and may help pathogenic Leptospira to escape complement-mediated clearance in human hosts. Indeed, NHS treated with Lsa23 confers a partial serum resistance phenotype to Leptospira biflexa, whereas blocking this protein with anti-Lsa23 renders pathogenic L. interrogans more susceptible to complement-mediated killing. Thus, Lsa23 is a multifunctional protein involved in many pathways, featuring C4b cleavage by plasmin, knowledge that may help in the development of preventive approaches to intervene with human complement escape by this versatile pathogen. (AU)

Processo FAPESP: 14/03792-8 - "avaliação da evasão do sistema imunológico por cepas patogênicas de Leptospira interrogans a nível da via terminal do sistema complemento"
Beneficiário:Gabriela Hase Siqueira
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 12/23913-9 - Identificação e caracterização de proteínas de Leptospira interrogans envolvidas nas interações patógeno - hospedeiro
Beneficiário:Ana Lucia Tabet Oller Do Nascimento
Linha de fomento: Auxílio à Pesquisa - Regular