Defect internalization and tyrosine kinase activation in Aire deficient antigen presenting cells exposed to Candida albicans antigens.
Patients with Autoimmune polyendocrine syndrome type I (APS I) present with multiple endocrine failures due to organ-specific autoimmune disease, thought to be T-cell-mediated. Paradoxically, APS I patients suffer from chronic mucocutaneous candidiasis. The mutated gene has been identified as the Autoimmune regulator (AIRE). Aire is expressed in medullary epithelial cells of the thymus and in antigen presenting cells in the periphery. T cells from Aire deficient mice and men displayed an enhanced proliferative response against Candida antigen in vitro, suggesting that Aire deficient T cells are competent in recognizing Candida albicans. In contrast, monocytes from APS I patients displayed a decreased and delayed internalization of zymosan. Furthermore, Candida antigen activated monocytes from APS I patients show decreased and altered phoshotyrosine kinase activation. In conclusion, Aire deficient APCs have a defect receptor mediated internalization of Candida which affects kinase activation, likely altering the innate Candida immune response.
Brännström
Johan
J
Karolinska Institutet, Department of Medicine, Unit of Clinical Allergy Research L2:04, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
Hässler
Signe
S
Peltonen
Leena
L
Herrmann
Björn
B
Winqvist
Ola
O
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D000946:Antigens, Fungal / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology*; D002457:Cell Extracts; D049109:Cell Proliferation; D002473:Cell Wall / Q000276:immunology; D002478:Cells, Cultured; D004789:Enzyme Activation; D005260:Female; D005656:Fungal Proteins / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015054:Zymosan / Q000276:immunology; D000096927:AIRE Protein
D000946:Antigens, Fungal; D002457:Cell Extracts; D005656:Fungal Proteins; D011505:Protein-Tyrosine Kinases; D014157:Transcription Factors; D015054:Zymosan; D000096927:AIRE Protein