Beta-Interferon Needed for a Healthy Immune Response
Beta-interferon is required for proper identification of an invader, including any virus, so that higher-powered immune troops can mount a targeted response.
Study Title: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.
From press release:
Researchers from the Molecular Immunology group at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany have now shown that Beta-Interferon also plays a crucial role during an immune response: without Beta-Interferon immune cells are unable to show “wanted posters” of pathogens to other cells. As a consequence, these cells will not recognize the pathogen and the immune response does not start properly.
During an infection, immune cells produce Beta-Inferferon. Interestingly, an immune response is even stronger when a low amount of Beta-Interferon has already been present before the infection occurs. Scientists call this behaviour “priming”. A healthy basal level of Beta-Interferon facilitates a faster immune reaction against microbial and viral threads.
Researchers from the HZI have now managed to show why this is the case: Beta-Interferon is a key regulator and of vital importance in enabling the immune system to display fragments of pathogens, so-called antigens. Immune cells present these antigens on their surface and in this way communicate with one another: antigens are the “wanted posters” of the virus or the bacterium which has to be destroyed.
The researchers discovered the important role of Beta-Interferon in mice lacking the gene for Beta-Interferon. These mice displayed poor immune responses. “Without those knock-out mice we would not have been able to identify the impact of Beta-Interferon on the immune system,” says Siegfried Weiß, leader of the Molecular Immunology group at the HZI. His research assistant, the scientist Natalia Zietara, investigated what Beta-Interferon is doing in immune cells. She found a molecular factor that is pivotal in producing the pathogen’s profile and which is regulated by Beta-Interferon. The factor belongs to a group of proteins that is usually produced in conditions of stress. Without Beta-Interferon, no active stress protein – without stress protein, no wanted poster – without wanted poster, no immune response.
“We now have a far better understanding of how immune responses start, but also how diseases like autoimmune diseases may develop,” says Weiß: without Beta-Interferon, the immune system may not be able to learn how to tolerate itself during the embryonic phase and that it should not fight against self-structures. “Our findings can help to develop or improve new therapeutics to combat autoimmune diseases such as multiple sclerosis or cancer.”
1.Zietara N, Łyszkiewicz M, Gekara N, Puchałka J, Dos Santos VA, Hunt CR, Pandita TK, Lienenklaus S, Weiss S. Absence of IFN-beta impairs antigen presentation capacity of splenic dendritic cells via down-regulation of heat shock protein 70 J Immunol. 2009 July 183(2):1099-109.
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