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A critical role for CARD9 in pneumocystis pneumonia host defence.
Kottom, Theodore J; Nandakumar, Vijayalakshmi; Hebrink, Deanne M; Carmona, Eva M; Limper, Andrew H.
Afiliación
  • Kottom TJ; Department of Pulmonary and Critical Care Medicine, Division of Thoracic Diseases Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • Nandakumar V; Department of Pulmonary and Critical Care Medicine, Division of Thoracic Diseases Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • Hebrink DM; Department of Pulmonary and Critical Care Medicine, Division of Thoracic Diseases Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • Carmona EM; Department of Pulmonary and Critical Care Medicine, Division of Thoracic Diseases Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
  • Limper AH; Department of Pulmonary and Critical Care Medicine, Division of Thoracic Diseases Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Cell Microbiol ; 22(10): e13235, 2020 10.
Article en En | MEDLINE | ID: mdl-32548948
Caspase recruitment domains-containing protein 9 (CARD9) is an adaptor molecule critical for key signalling pathways initiated through C-type lectin receptors (CLRs). Previous studies demonstrated that Pneumocystis organisms are recognised through a variety of CLRs. However, the role of the downstream CARD9 adaptor signalling protein in host defence against Pneumocystis infection remains to be elucidated. Herein, we analysed the role of CARD9 in host defence against Pneumocystis both in CD4-depleted CARD9-/- and immunocompetent hosts. Card9 gene-disrupted (CARD9-/- ) mice were more susceptible to Pneumocystis, as evidenced by reduced fungal clearance in infected lungs compared to wild-type (WT) infected mice. Our data suggests that this defect was due to impaired proinflammatory responses. Furthermore, CARD9-/- macrophages were severely compromised in their ability to differentiate and express M1 and M2 macrophage polarisation markers, to enhanced mRNA expression for Dectin-1 and Mincle, and most importantly, to kill Pneumocystis in vitro. Remarkably, compared to WT mice, and despite markedly increased organism burdens, CARD9-/- animals did not exhibit worsened survival during pneumocystis pneumonia (PCP), perhaps related to decreased lung injury due to altered influx of inflammatory cells and decreased levels of proinflammatory cytokines in response to the organism. Finally, although innate phase cytokines were impaired in the CARD9-/- animals during PCP, T-helper cell cytokines were normal in immunocompetent CARD9-/- animals infected with Pneumocystis. Taken together, our data demonstrate that CARD9 has a critical function in innate immune responses against Pneumocystis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pneumocystis / Neumonía por Pneumocystis / Macrófagos Alveolares / Pneumocystis carinii / Proteínas Adaptadoras de Señalización CARD Límite: Animals Idioma: En Revista: Cell Microbiol Asunto de la revista: MICROBIOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: India
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pneumocystis / Neumonía por Pneumocystis / Macrófagos Alveolares / Pneumocystis carinii / Proteínas Adaptadoras de Señalización CARD Límite: Animals Idioma: En Revista: Cell Microbiol Asunto de la revista: MICROBIOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: India