Type I IFN signaling in CD8- DCs impairs Th1-dependent malaria immunity.
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Best, Shannon E
Montes de Oca, Marcela
James, Kylie R
Edwards, Chelsea L
de Labastida Rivera, Fabian
Amante, Fiona H
Bunn, Patrick T
Hertzog, Paul J
Gun, Sin Yee
MacDonald, Kelli P A
Hill, Geoffrey R
Engwerda, Christian R
MetadataShow full item record
AbstractMany 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.
CitationType I IFN signaling in CD8- DCs impairs Th1-dependent malaria immunity. 2014, 124 (6):2483-96 J. Clin. Invest.
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- Type I interferons suppress CD4⁺ T-cell-dependent parasite control during blood-stage Plasmodium infection.
- Authors: Haque A, Best SE, Ammerdorffer A, Desbarrieres L, de Oca MM, Amante FH, de Labastida Rivera F, Hertzog P, Boyle GM, Hill GR, Engwerda CR
- Issue date: 2011 Sep
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