RGD Reference Report - CCR7 deficiency on dendritic cells enhances fungal clearance in a murine model of pulmonary invasive aspergillosis. - Rat Genome Database

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CCR7 deficiency on dendritic cells enhances fungal clearance in a murine model of pulmonary invasive aspergillosis.

Authors: Hartigan, AJ  Westwick, J  Jarai, G  Hogaboam, CM 
Citation: Hartigan AJ, etal., J Immunol. 2009 Oct 15;183(8):5171-9. Epub 2009 Sep 25.
RGD ID: 5130908
Pubmed: (View Article at PubMed) PMID:19783686
DOI: Full-text: DOI:10.4049/jimmunol.0901027

Aspergillus fumigatus is a sporulating fungus found ubiquitously in the environment and is easily cleared from immunocompetent hosts. Invasive aspergillosis develops in immunocompromised patients, and is a leading cause of mortality in hematopoietic stem cell transplant recipients. CCR7 and its ligands, CCL19 and CCL21, are responsible for the migration of dendritic cells from sites of infection and inflammation to secondary lymphoid organs. To investigate the role of CCR7 during invasive aspergillosis, we used a well-characterized neutropenic murine model. During invasive aspergillosis, mice with a CCR7 deficiency in the hematopoietic compartment exhibited increased survival and less pulmonary injury compared with the appropriate wild-type control. Flow cytometric analysis of the chimeric mice revealed an increase in the number of dendritic cells present in the lungs of CCR7-deficient chimeras following infection with Aspergillus conidia. An adoptive transfer of dendritic cells into neutropenic mice provided a protective effect during invasive aspergillosis, which was further enhanced with the adoptive transfer of CCR7-deficient dendritic cells. Additionally, CCR7-deficient dendritic cells activated in vitro with Aspergillus conidia expressed higher TNF-alpha, CXCL10, and CXCL2 levels, indicating a more activated cellular response to the fungus. Our results suggest that the absence of CCR7 is protective during invasive aspergillosis in neutropenic mice. Collectively, these data demonstrate a potential deleterious role for CCR7 during primary immune responses directed against A. fumigatus.

Annotation

Disease Annotations    
aspergillosis  (IEP,IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Ccl19  (C-C motif chemokine ligand 19)
Ccr7  (C-C motif chemokine receptor 7)

Genes (Mus musculus)
Ccl19  (chemokine (C-C motif) ligand 19)
Ccr7  (chemokine (C-C motif) receptor 7)

Genes (Homo sapiens)
CCL19  (C-C motif chemokine ligand 19)
CCR7  (C-C motif chemokine receptor 7)


Additional Information