Affiliation:
1. Departamento de Microbiologia/Laboratório de Micologia Universidade Federal de Minas Gerais Belo Horizonte Brazil
2. Departamento de Bioquímica e Imunologia Universidade Federal de Minas Gerais Belo Horizonte Brazil
3. Pulmonary and Critical Care Medicine Division, Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts USA
4. Departamento de Patologia/Laboratório de Patologia Celular e Molecular Universidade Federal de Minas Gerais Belo Horizonte Brazil
Abstract
AbstractMicroorganisms that cause pneumonia and translocate to the central nervous system (CNS) are responsible for high mortality worldwide. The fungus Cryptococcus gattii (Cg) and the bacteria Streptococcus pneumoniae (Sp) target the same infection organs. This study aimed to investigate the consequences of secondary Sp infection during murine cryptococcosis. Mice infected with Sp after Cg showed significantly increased lethality and a drop in scores of motor behaviour, neuropsychiatric status and autonomous function. Previous Cg infection favoured Sp multiplication in the lungs, causing intense inflammation and necrosis, with further increased bacterial translocation to the spleen, liver and brain. This phenotype was associated with increased platelet‐activating factor receptor (Pafr) gene expression, reduced M1 macrophage recruitment, and high levels of proinflammatory mediators. Strategies to overcome early mortality (i.e., infection of Pafr−/− mice, treatment with IL‐1 inhibitor or corticoid) were insufficient to revert this phenotype. These results suggest that Cg infection makes the lung microenvironment favourable for Sp colonization and dissemination. Altogether, it leads to an exacerbated and ineffective inflammatory response, decisive for the increased morbidity and mortality during coinfection. In conclusion, our results highlight the importance of more studies addressing coinfections and their consequences in the host, aiming to establish more effective therapeutical strategies.
Funder
Ministério da Saúde
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Fundação de Amparo à Pesquisa do Estado de Minas Gerais
Subject
Immunology,Immunology and Allergy
Cited by
1 articles.
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