Human dendritic cells following Aspergillus fumigatus infection express the CCR7 receptor and a differential pattern of interleukin-12 (IL-12), IL-23, and IL-27 cytokines, which lead to a Th1 response.
Aspergillus fumigatus is the most prevalent airborne fungal pathogen and causes fatal invasive aspergillosis in immunocompromised patients. Given the essential role of dendritic cells (DC) in initiating and regulating immune responses, we investigated the impact of A. fumigatus conidial infection on human DC. A. fumigatus conidia were rapidly internalized and induced the release of tumor necrosis factor alpha within the first 8 h. After A. fumigatus infection, the majority of DC underwent full maturation, although CCR7 expression was observed only in DC that had internalized the conidia. Additionally, the analysis of regulatory cytokines showed that infected DC simultaneously produced interleukin-12p70 (IL-12p70) and significant amounts of IL-10. IL-10 neutralization was not able to further increase IL-12p70 production from infected DC. Whereas the central role of IL-12 in the generation of Th1 cells has long been appreciated, recently two other members of the IL-12 family, IL-23 and IL-27, were reported to play important roles in the regulation of gamma interferon (IFN-gamma) production from naïve and memory T cells. A. fumigatus-infected DC were also able to express high levels of IL-23p19 and low levels of IL-27p28 at later stages of infection. According to this expression pattern, A. fumigatus-infected DC were able to prime IFN-gamma production of naïve T cells. Thus, this study on the expression of the new IL-12 family members controlling the Th1 response sheds light on a novel aspect of the contribution of DC to anti-Aspergillus immunity.
Department of Infectious, Parasitic, and Immuno-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Valérie
V
Gafa
Roberto
R
Lande
Maria Cristina
MC
Gagliardi
Martina
M
Severa
Elena
E
Giacomini
Maria Elena
ME
Remoli
Roberto
R
Nisini
Carlo
C
Ramoni
Paolo
P
Di Francesco
Delphine
D
Aldebert
Renée
R
Grillot
Eliana M
EM
Coccia
D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000032:analysis*; D003713:Dendritic Cells / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D018664:Interleukin-12 / Q000032:analysis / Q000378:metabolism; D020381:Interleukin-17 / Q000032:analysis / Q000378:metabolism; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000032:analysis / Q000378:metabolism; D008213:Lymphocyte Activation; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*
C515370:CCR7 protein, human; D016207:Cytokines; C464462:IL17D protein, human; C508840:IL23A protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D018664:Interleukin-12