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Type I IFN signaling in CD8- DCs impairs Th1-dependent malaria immunity.
- Source :
-
Journal of Clinical Investigation . Jun2014, Vol. 124 Issue 6, p2483-2496. 14p. 6 Color Photographs, 1 Black and White Photograph. - Publication Year :
- 2014
-
Abstract
- Many pathogens, including viruses, bacteria, and protozoan parasites, suppress cellular immune responses through activation of type I IFN signaling. Recent evidence suggests that immune suppression and susceptibility to the malaria parasite, Plasmodium, is mediated by type I IFN; however, it is unclear how type I IFN suppresses immunity to blood-stage Plasmodium parasites. During experimental severe malaria, CD4+ Th cell responses are suppressed, and conventional DC (cDC) function is curtailed through unknown mechanisms. Here, we tested the hypothesis that type I IFN signaling directly impairs cDC function during Plasmodium infection in mice. Using cDC-specific IFNAR1-deficient mice, and mixed BM chimeras, we found that type I IFN signaling directly affects cDC function, limiting the ability of cDCs to prime IFN-γ--producing Th1 cells. Although type I IFN signaling modulated all subsets of splenic cDCs, CD8- cDCs were especially susceptible, exhibiting reduced phagocytic and Th1-promoting properties in response to type I IFNs. Additionally, rapid and systemic IFN-α production in response to Plasmodium infection required type I IFN signaling in cDCs themselves, revealing their contribution to a feed-forward cytokine-signaling loop. Together, these data suggest abrogation of type I IFN signaling in CD8- splenic cDCs as an approach for enhancing Th1 responses against Plasmodium and other type I IFN--inducing pathogens. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CD8 antigen
*MALARIA
*IMMUNE response
*IMMUNOSUPPRESSION
*PLASMODIUM
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 124
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- 96418999
- Full Text :
- https://doi.org/10.1172/JCI70698