Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2007 Jun-Jul;89(6-7):843-55.
doi: 10.1016/j.biochi.2007.04.018. Epub 2007 May 8.

The role of type I interferon production by dendritic cells in host defense

P Fitzgerald-Bocarsly  1 , D Feng
Affiliations
Review

The role of type I interferon production by dendritic cells in host defense

P Fitzgerald-Bocarsly et al. Biochimie. 2007 Jun-Jul.

Abstract

Type I interferons (IFN) and dendritic cells (DC) share an overlapping history, with rapidly accumulating evidence for vital roles for both production of type 1 IFN by DC and the interaction of this IFN both with DC and components of the innate and adaptive immune responses. Within the innate immune response, the plasmacytoid DC (pDC) are the "professional" IFN producing cells, expressing specialized toll-like receptors (TLR7 and -9) and high constitutive expression of IRF-7 that allow them to respond to viruses with rapid and extremely robust IFN production; following activation and production of IFN, the pDC subsequently mature into antigen presenting cells that help to shape the adaptive immune response. However, like most cells in the body, the myeloid or conventional DC (mDC or cDC) also produce type I IFNs, albeit typically at a lower level than that observed with pDC, and this IFN is also important in innate and adaptive immunity induced by these classic antigen presenting cells. These two major DC subsets and their IFN products interact both with each other as well as with NK cells, monocytes, T helper cells, T cytotoxic cells, T regulatory cells and B cells to orchestrate the early immune response. This review discusses some of the converging history of DC and IFN as well as mechanisms for IFN induction in DC and the effects of this IFN on the developing immune response.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Type I IFN production pathways in human pDC and cDC/mDC
pDC utilize a variety of cell-surface receptors to endocytose viruses into endosomes where the viral nucleic acid is uncoated. There, the RNA or DNA interacts with TLR7 and -9, respectively, to induce type I IFN gene expression independent of viral replication and in a MyD88-dependent manner. pDC express high constitutive levels of the transcription factor, IRF-7 that is required for the induction of IFN-α. cDC also utilize a TLR-dependent pathway for the sensing of viral RNA – TLR3, which recognizes dsRNA within the endosomes. This IFN response, however, requires autocrine IFN feedback to upregulate IRF-7 expression to get the full range of IFN subtype expression. In addition to the TLR-dendent IFN induction, both types of DC have MyD88 independent mechanisms for recognition of cytoplasmic viruses following infection of the cells with virus, including the RIG-I system for recognition of cytoplasmic dsRNA and an as yet undefined cytoplasmic sensor for DNA.
Figure 2
Figure 2. DC-derived IFN induces DC subset interaction and influences innate and adaptive immune responses
Type I IFN produced in response to virus by pDC (and in some cases cDC) leads to antiviral activity, recruitment and upregulation of NK activity, activation of monocytes as well as activation and maturation of cDC. Depending on the nature of the stimulus received, the mDC and pDC have the capacity to activate B cells for the production of antibody and activate Th1, Th2, Treg and CD8+ T cell activity and T memory, with IFN-α playing a central role in these activities.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Isaacs A, Lindenmann J. Virus interference. 1. The interferon. Proc Royal Society Biology. 1957;147:258. - PubMed
    1. Ronnblom L, Ramstedt U, Alm GV. Properties of human natural interferon-producing cells stimulated by tumor cell lines. European Journal of Immunology. 1983;13:471–476. - PubMed
    1. Cederblad B, Alm G. Infrequent but efficient interferon-α-producing human mononuclear leukocytes induced by herpes simplex virus in vitro studies by immunoplaque and limiting dilution assays. J Interferon Res. 1990;10:65–73. - PubMed
    1. Perussia B, Fanning V, Trinchieri G. A leukocyte subset bearing HLA-DR antigens is responsible for in vitro alpha interferon production in response to viruses. Nat Immun Cell-Growth Regul. 1985;4:120–137. - PubMed
    1. Fitzgerald-Bocarsly P, Feldman M, Mendelsohn M, Curl S, Lopez C. Human mononuclear cells which produce interferon-alpha during NK (HSV-FS) assays are HLA-DR positive cells distinct from cytolytic natural killer effectors. J Leukocyte Biol. 1988;43:323–334. - PubMed

LinkOut - more resources