Human Invariant Natural Killer T cells possess immune-modulating functions during Aspergillus infection.
Aspergillus fumigatus is the most common cause for invasive fungal infections, a disease associated with high mortality in immune-compromised patients. CD1d-restricted invariant natural killer T (iNKT) cells compose a small subset of T cells known to impact the immune response toward various infectious pathogens. To investigate the role of human iNKT cells during A. fumigatus infection, we studied their activation as determined by CD69 expression and cytokine production in response to distinct fungal morphotypes in the presence of different CD1d(+) antigen presenting cells using flow cytometry and multiplex enzyme-linked immunosorbent assay (ELISA). Among CD1d(+) subpopulations, CD1d(+)CD1c(+) mDCs showed the highest potential to activate iNKT cells on a per cell basis. The presence of A. fumigatus decreased this effect of CD1d(+)CD1c(+) mDCs on iNKT cells and led to reduced secretion of TNF-α, G-CSF and RANTES. Production of other Th1 and Th2 cytokines was not affected by the fungus, suggesting an immune-modulating function for human iNKT cells during A. fumigatus infection.
Medizinische Klinik und Poliklinik II, University Hospital Wuerzburg, Wuerzburg, Germany.
Antonia
A
Beitzen-Heineke
Medizinische Klinik und Poliklinik II, University Hospital Wuerzburg, Wuerzburg, Germany.
Maria
M
Bouzani
Medizinische Klinik und Poliklinik II, University Hospital Wuerzburg, Wuerzburg, Germany.
Anna-Lena
AL
Schmitt
Septomics Research Centre, Friedrich-Schiller-University Jena and Leibniz-Institute for Natural Products Research and Infection Biology - Hans Knoell Institute, Jena, Germany.
Oliver
O
Kurzai
Septomics Research Centre, Friedrich-Schiller-University Jena and Leibniz-Institute for Natural Products Research and Infection Biology - Hans Knoell Institute, Jena, Germany.
Kerstin
K
Hünniger
Medizinische Klinik und Poliklinik II, University Hospital Wuerzburg, Wuerzburg, Germany.
Hermann
H
Einsele
Medizinische Klinik und Poliklinik II, University Hospital Wuerzburg, Wuerzburg, Germany loeffler_j@ukw.de.
Juergen
J
Loeffler
D000938:Antigen-Presenting Cells / Q000276:immunology / Q000382:microbiology; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis; D055610:Antigens, CD1d / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D056747:Immunomodulation; D037181:Lectins, C-Type / Q000032:analysis; D008213:Lymphocyte Activation; D055611:Natural Killer T-Cells / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D018949:Antigens, CD1; D055610:Antigens, CD1d; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D006023:Glycoproteins; D037181:Lectins, C-Type; D000099192:CD69 Antigens; C437944:CD1C protein, human; C526877:CD1D protein, human
Aspergillus fumigatus; CD1d+ cells; invariant natural killer T (iNKT) cells; mDCs