Absence of IFN-beta impairs antigen presentation capacity of splenic dendritic cells via down-regulation of heat shock protein 70.
Type I IFNs play a key role in linking the innate and adaptive arms of the immune system. Although produced rapidly in response to pathogens, IFNs are also produced at low levels in the absence of infection. In the present study, we demonstrate that constitutively produced IFNs are necessary in vivo to maintain dendritic cells in an "Ag presentation-competent" state. Conventional dendritic cells (cDCs) isolated from spleens of IFN-beta or IFNAR-deficient mice exhibit a highly impaired ability to present Ag and activate naive T cells. Microarray analysis of mRNA isolated from IFN-beta(-/-) and IFNAR(-/-) cDCs revealed diminished expression of two genes that encoded members of the heat shock protein 70 (Hsp70) family. Consistent with this observation, pharmacological inhibition of Hsp70 in cDCs from wild-type mice impaired their T cell stimulatory capacity. Similarly, the Ag presentation ability of splenic cDCs isolated from Hsp70.1/3(-/-) mice was also severely impaired in comparison to wild-type cDCs. Thus, constitutive IFN-beta expression regulates Hsp70 levels to help maintain dendritic cells in a competent state for efficient priming of effector T cells in vivo.
Zietara
Natalia
N
Department of Molecular Biotechnology, Molecular Immunology Group, Helmholtz Centre for Infection Research, HZI, Braunschweig, Germany. naz06@helmholtz-hzi.de
Łyszkiewicz
Marcin
M
Gekara
Nelson
N
Puchałka
Jacek
J
Dos Santos
Vitor A P Martins
VA
Hunt
Clayton R
CR
Pandita
Tej K
TK
Lienenklaus
Stefan
S
Weiss
Siegfried
S
D000818:Animals; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D018840:HSP70 Heat-Shock Proteins; D007155:Immunologic Factors; D016899:Interferon-beta / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology
D018840:HSP70 Heat-Shock Proteins; C508032:Ifnar1 protein, mouse; D007155:Immunologic Factors; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta