Cathelicidin Insufficiency in Patients with Fatal Leptospirosis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/18163 |
Resumo: | National Institute of Allergy and Infectious Diseases grants U01AI088752 (AIK), R01AI052473 (AIK), and R01 AI121207 (AIK) |
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Lindow, Janet CWunder Junior, Elsio AugustoPopper, Stephen JMin, Jin-NaMannam, PraveenSrivastava, AnupYao, YiHacker, Kathryn PRaddassi, KhadirLee, Patty JMontgomery, Ruth RShaw, Albert CHagan, Jose EAraújo, Guilherme CNery, NivisonRelman, David AKim, Charles CReis, Mitermayer Galvão dosKo, Albert Icksang2017-03-24T18:32:06Z2017-03-24T18:32:06Z2016LINDOW, J. C. et al. Cathelicidin Insufficiency in Patients with Fatal Leptospirosis. PLoS Pathogens, v. 12, n. 11, p. e1005943, 2016.1935-2727https://www.arca.fiocruz.br/handle/icict/1816310.1371/journal.ppat.1005943National Institute of Allergy and Infectious Diseases grants U01AI088752 (AIK), R01AI052473 (AIK), and R01 AI121207 (AIK)Yale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilYale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilStanford University School of Medicine. Department of Medicine. Stanford, California, USAYale University School of Medicine. Critical Care and Sleep Medicine. Section of Pulmonary. New Haven, Connecticut, USAYale University School of Medicine. Critical Care and Sleep Medicine. Section of Pulmonary. New Haven, Connecticut, USAYale University School of Medicine. Critical Care and Sleep Medicine. Section of Pulmonary. New Haven, Connecticut, USAYale School of Medicine. Department of Internal Medicine.Section of Rheumatology. New Haven, Connecticut, USAYale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USAYale School of Medicine. Department of Neurology. New Haven, Connecticut, USAYale University School of Medicine. Critical Care and Sleep Medicine. Section of Pulmonary. New Haven, Connecticut, USAYale School of Medicine. Department of Internal Medicine.Section of Rheumatology. New Haven, Connecticut, USAYale School of Medicine. Department of Internal Medicine. Section of Infectious Diseases. New Haven, Connecticut, USAYale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilStanford University School of Medicine. Department of Medicine. Stanford, California, USA / Stanford University School of Medicine. Department of Microbiology and Immunology. Stanford, California, USAUniversity of California. Department of Medicine. Division of Experimental Medicine. San Francisco, California, USAFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilYale School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilLeptospirosis causes significant morbidity and mortality worldwide; however, the role of the host immune response in disease progression and high case fatality (>10-50%) is poorly understood. We conducted a multi-parameter investigation of patients with acute leptospirosis to identify mechanisms associated with case fatality. Whole blood transcriptional profiling of 16 hospitalized Brazilian patients with acute leptospirosis (13 survivors, 3 deceased) revealed fatal cases had lower expression of the antimicrobial peptide, cathelicidin, and chemokines, but more abundant pro-inflammatory cytokine receptors. In contrast, survivors generated strong adaptive immune signatures, including transcripts relevant to antigen presentation and immunoglobulin production. In an independent cohort (23 survivors, 22 deceased), fatal cases had higher bacterial loads (P = 0.0004) and lower anti-Leptospira antibody titers (P = 0.02) at the time of hospitalization, independent of the duration of illness. Low serum cathelicidin and RANTES levels during acute illness were independent risk factors for higher bacterial loads (P = 0.005) and death (P = 0.04), respectively. To investigate the mechanism of cathelicidin in patients surviving acute disease, we administered LL-37, the active peptide of cathelicidin, in a hamster model of lethal leptospirosis and found it significantly decreased bacterial loads and increased survival. Our findings indicate that the host immune response plays a central role in severe leptospirosis disease progression. While drawn from a limited study size, significant conclusions include that poor clinical outcomes are associated with high systemic bacterial loads, and a decreased antibody response. Furthermore, our data identified a key role for the antimicrobial peptide, cathelicidin, in mounting an effective bactericidal response against the pathogen, which represents a valuable new therapeutic approach for leptospirosis.engPublic Library of ScienceLeptospiroseCatelicidinaHumanoFatores de RiscoBactericidaSobrevidaLeptospirosisCathelicidinHumanRisk factorsBactericidalSurvivalCathelicidin Insufficiency in Patients with Fatal Leptospirosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/18163/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALLindow JC Cathelicidin ....pdfLindow JC Cathelicidin 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| dc.title.pt_BR.fl_str_mv |
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis |
| title |
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis |
| spellingShingle |
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis Lindow, Janet C Leptospirose Catelicidina Humano Fatores de Risco Bactericida Sobrevida Leptospirosis Cathelicidin Human Risk factors Bactericidal Survival |
| title_short |
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis |
| title_full |
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis |
| title_fullStr |
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis |
| title_full_unstemmed |
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis |
| title_sort |
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis |
| author |
Lindow, Janet C |
| author_facet |
Lindow, Janet C Wunder Junior, Elsio Augusto Popper, Stephen J Min, Jin-Na Mannam, Praveen Srivastava, Anup Yao, Yi Hacker, Kathryn P Raddassi, Khadir Lee, Patty J Montgomery, Ruth R Shaw, Albert C Hagan, Jose E Araújo, Guilherme C Nery, Nivison Relman, David A Kim, Charles C Reis, Mitermayer Galvão dos Ko, Albert Icksang |
| author_role |
author |
| author2 |
Wunder Junior, Elsio Augusto Popper, Stephen J Min, Jin-Na Mannam, Praveen Srivastava, Anup Yao, Yi Hacker, Kathryn P Raddassi, Khadir Lee, Patty J Montgomery, Ruth R Shaw, Albert C Hagan, Jose E Araújo, Guilherme C Nery, Nivison Relman, David A Kim, Charles C Reis, Mitermayer Galvão dos Ko, Albert Icksang |
| author2_role |
author author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Lindow, Janet C Wunder Junior, Elsio Augusto Popper, Stephen J Min, Jin-Na Mannam, Praveen Srivastava, Anup Yao, Yi Hacker, Kathryn P Raddassi, Khadir Lee, Patty J Montgomery, Ruth R Shaw, Albert C Hagan, Jose E Araújo, Guilherme C Nery, Nivison Relman, David A Kim, Charles C Reis, Mitermayer Galvão dos Ko, Albert Icksang |
| dc.subject.other.pt_BR.fl_str_mv |
Leptospirose Catelicidina Humano Fatores de Risco Bactericida Sobrevida |
| topic |
Leptospirose Catelicidina Humano Fatores de Risco Bactericida Sobrevida Leptospirosis Cathelicidin Human Risk factors Bactericidal Survival |
| dc.subject.en.pt_BR.fl_str_mv |
Leptospirosis Cathelicidin Human Risk factors Bactericidal Survival |
| description |
National Institute of Allergy and Infectious Diseases grants U01AI088752 (AIK), R01AI052473 (AIK), and R01 AI121207 (AIK) |
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2016 |
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2016 |
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2017-03-24T18:32:06Z |
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2017-03-24T18:32:06Z |
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LINDOW, J. C. et al. Cathelicidin Insufficiency in Patients with Fatal Leptospirosis. PLoS Pathogens, v. 12, n. 11, p. e1005943, 2016. |
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https://www.arca.fiocruz.br/handle/icict/18163 |
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1935-2727 |
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10.1371/journal.ppat.1005943 |
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LINDOW, J. C. et al. Cathelicidin Insufficiency in Patients with Fatal Leptospirosis. PLoS Pathogens, v. 12, n. 11, p. e1005943, 2016. 1935-2727 10.1371/journal.ppat.1005943 |
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