Heparin-Binding Protein Release Is Strongly Induced by Leptospira Species and Is a Candidate for an Early Diagnostic Marker of Human Leptospirosis

Autor(es)

Vieira, Monica L. ^{[1, 2]} ; Persson, Sandra ^[1] ; Lopes-Ferreira, Monica ^[3] ; Romero, Eliete C. ^[4] ; Kirchgatter, Karin ^[5] ; Nascimento, Ana Lucia T. O. ^[2] ; Herwald, Heiko ^[1]

Afiliação do(s) autor(es)

^[1] Lund Univ, Div Infect Med, Dept Clin Sci, Lund - Sweden

^[2] Inst Butantan, Lab Especial Desenvolvimento Vacinas, Sao Paulo - Brazil

^[3] Inst Butantan, Lab Especial Toxinol Aplicada, Sao Paulo - Brazil

^[4] Adolfo Lutz Inst, Ctr Bacteriol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Med Trop Sao Paulo, Superintendencia Controle Endemias, Nucleo Estudos Malaria, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Infectious Diseases; v. 219, n. 6, p. 996-1006, MAR 15 2019.
• Citações Web of Science: 0

Resumo

Here we show that heparin-binding protein (HBP) can be used as an early biomarker in patients with leptospirosis. Our experiments further suggest that leptospiral proteins are able to release HBP to an extent that the vascular barrier is impaired.Leptospirosis, caused by spirochetes of the genus Leptospira, is one of the most widespread zoonoses worldwide. Efficient diagnostic methods for early diagnosis of leptospirosis are still lacking, and acute disease presents with nonspecific symptomatology and is often misdiagnosed. The leptospires pathogenic processes and virulence mechanisms remain virtually unknown. In severe infections, hemostatic impairment is frequently observed, and pathophysiological complications often develop when the host response is modulated by the pathogen. The neutrophil heparin-binding protein (HBP) is an inflammatory mediator and potent inducer of vascular leakage. In this study, we found that leptospires and their secreted products induce the release of HBP from stimulated neutrophils through a controlled degranulation mechanism. We acknowledged 2 leptospiral proteins as able to induce HBP degranulation. These findings have clinical implications, as high levels of HBP were detected in serum from patients with leptospirosis, especially at the early phase of the disease. In conclusion, we describe a new mechanism by which the leptospirosis pathophysiological complications may arise, such as vascular leakage and edema formation. We also propose HBP as a new early screening biomarker for human leptospirosis. (AU)

• Processo FAPESP: 18/07054-2 - As plaquetas na interface da modulação da imunidade, inflamação e hemostasia na leptospirose
• Beneficiário: Mônica Larucci Vieira
• Linha de fomento: Bolsas no Brasil - Apoio a Jovens Pesquisadores
• Processo FAPESP: 14/50981-0 - Busca de proteínas de superfície nas sequências do genoma da Leptospira interrogans: caracterização funcional e imunológica para o entendimento de mecanismos envolvidos na patogênese de bactéria
• Beneficiário: Ana Lucia Tabet Oller Do Nascimento
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/18337-4 - Modulation of hosts' coagulation and inflammation by Leptospira
• Beneficiário: Mônica Larucci Vieira
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado