Author | Dallmann-Sauer, Monica | |
Author | Xu, Yong Zhong | |
Author | Costa, Ana Lúcia França da | |
Author | Tao, Shao | |
Author | Gomes, Tiago Araujo | |
Author | Prata, Rhana Berto da Silva | |
Author | Correa- Macedo, Wilian | |
Author | Manry, Jérémy | |
Author | Alcaïs, Alexandre | |
Author | Abel, Laurent | |
Author | Cobat, Aurélie | |
Author | Fava, Vinicius M. | |
Author | Pinheiro, Roberta Olmo | |
Author | Lara, Flavio Alves | |
Author | Probst, Christian Macagnan | |
Author | Mira, Marcelo T. | |
Author | Schurr, Erwin | |
Access date | 2023-05-24T17:14:55Z | |
Available date | 2023-05-24T17:14:55Z | |
Document date | 2023 | |
Citation | DALLMANN-SAUER, Monica et al. Allele-dependent interaction of LRRK2 and NOD2 in leprosy. PLoS Pathog, v. 19, n. 3, p. 1-32, 2023. | en_US |
ISSN | 1553-7374 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/58625 | |
Language | por | en_US |
Publisher | Public Library of Science | en_US |
Rights | open access | en_US |
Subject in Portuguese | Proteína LRRK2 | en_US |
Title | Allele-dependent interaction of LRRK2 and NOD2 in leprosy | en_US |
Type | Article | en_US |
DOI | https://doi. org/10.1371/journal.ppat.1011260 | |
Abstract | Leprosy, caused by Mycobacterium leprae, rarely affects children younger than 5 years. Here, we studied a multiplex leprosy family that included monozygotic twins aged 22 months suffering from paucibacillary leprosy. Whole genome sequencing identified three amino acid mutations previously associated with Crohn’s disease and Parkinson’s disease as candidate variants for early onset leprosy: LRRK2 N551K, R1398H and NOD2 R702W. In genome-edited macrophages, we demonstrated that cells expressing the LRRK2 mutations displayed reduced apoptosis activity following mycobacterial challenge independently of NOD2. However, employing co-immunoprecipitation and confocal microscopy we showed that LRRK2 and NOD2 proteins interacted in RAW cells and monocyte-derived macrophages, and that this interaction was substantially reduced for the NOD2 R702W mutation. Moreover, we observed a joint effect of LRRK2 and NOD2 variants on Bacillus Calmette-Guérin (BCG)-induced respiratory burst, NF-κB activation and cytokine/chemokine secretion with a strong impact for the genotypes found in the twins consistent with a role of the identified mutations in the development of early onset leprosy. | en_US |
Affilliation | Program in Infectious Diseases and Immunity in Global Health. The Research Institute of the McGill University Health Centre. Montreal, Canada. / McGill International TB Centre. McGill University. Montreal, Canada. / Departments of Human Genetics and Medicine. Faculty of Medicine and Health Science. McGill University. Montreal, Canada. / Pontifícia Universidade Católica do Paraná. Escola de Medicina e Ciências da Vida. Programa de Pós-Graduação em Ciências da Saúde. Curitiba, PR, Brasil. | en_US |
Affilliation | Program in Infectious Diseases and Immunity in Global Health. The Research Institute of the McGill University Health Centre. Montreal, Canada. / McGill International TB Centre. McGill University. Montreal, Canada. | en_US |
Affilliation | Universidade Federal do Piauí. Centro de Ciências da Saúde. Departamento de Medicina Especializada. Teresina, PI, Brasil. | en_US |
Affilliation | Division of Experimental Medicine. Faculty of Medicine. McGill University. Montreal, Canada. / The Translational Research in Respiratory Diseases Program. The Research Institute of the McGill University Health Centre. Montreal, Canada. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Leprosia. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Program in Infectious Diseases and Immunity in Global Health. The Research Institute of the McGill University Health Centre. Montreal, Canada. / McGill International TB Centre. McGill University. Montreal, Canada. / Department of Biochemistry. Faculty of Medicine and Health Science. McGill University. Montreal, Canada. | en_US |
Affilliation | Program in Infectious Diseases and Immunity in Global Health. The Research Institute of the McGill University Health Centre. Montreal, Canada. / McGill International TB Centre. McGill University. Montreal, Canada. | en_US |
Affilliation | Laboratory of Human Genetics of Infectious Diseases. Necker Branch. Institut National de la Santé et de la Recherche Médicale. Paris, France. / Université Paris Cité. Imagine Institute. Paris, France. | en_US |
Affilliation | Laboratory of Human Genetics of Infectious Diseases. Necker Branch. Institut National de la Santé et de la Recherche Médicale. Paris, France. / Université Paris Cité. Imagine Institute. Paris, France. / St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University. New York, United States of America. | en_US |
Affilliation | Laboratory of Human Genetics of Infectious Diseases. Necker Branch. Institut National de la Santé et de la Recherche Médicale. Paris, France. / Université Paris Cité. Imagine Institute. Paris, France. / St. Giles Laboratory of Human Genetics of Infectious Diseases. Rockefeller Branch. Rockefeller University. New York, United States of America. | en_US |
Affilliation | Program in Infectious Diseases and Immunity in Global Health. The Research Institute of the McGill University Health Centre. Montreal, Canada. / McGill International TB Centre. McGill University. Montreal, Canada. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Leprosia. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Molecular e Sistêmica de Tripanossomatídeos. Curitiba, PR, Brasil. | en_US |
Affilliation | Pontifícia Universidade Católica do Paraná. Escola de Medicina e Ciências da Vida. Programa de Pós-Graduação em Ciências da Saúde. Curitiba, PR, Brasil. | en_US |
Affilliation | Program in Infectious Diseases and Immunity in Global Health. The Research Institute of the McGill University Health Centre. Montreal, Canada. / McGill International TB Centre. McGill University. Montreal, Canada. / Department of Biochemistry. Faculty of Medicine and Health Science. McGill University. Montreal, Canada. | en_US |
Subject | Leprosy, Paucibacillary | en_US |
Subject | Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 | en_US |
Subject | Nod2 Signaling Adaptor Protein | en_US |
Subject | Mycobacterium bovis | en_US |
Subject in Spanish | Lepra Paucibacilar | en_US |
Subject in Spanish | Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina | en_US |
Subject in Spanish | Proteína Adaptadora de Señalización NOD2 | en_US |
Subject in French | Lèpre paucibacillaire | en_US |
Subject in French | Leucine-rich repeat serine-threonine protein kinase-2 | en_US |
Subject in French | Protéine adaptatrice de signalisation NOD2 | en_US |
DeCS | Hanseníase Paucibacilar | en_US |
DeCS | Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina | en_US |
DeCS | Proteína Adaptadora de Sinalização NOD2 | en_US |
DeCS | Bacillus Calmette-Guérin | en_US |