Flt3 permits survival during infection by rendering dendritic cells competent to activate NK cells

Eidenschenk, Céline; Crozat, Karine; Krebs, Philippe; Arens, Ramon; Popkin, Daniel L.; Arnold, Carrie; Blasius, Amanda L.; Benedict, Chris A.; Moresco, Eva Marie Y.; Xia, Yu; Beutler, Bruce

doi:10.1073/pnas.1005186107

Cited by 40 publications

(34 citation statements)

References 30 publications

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“…5A and B). As seen previously, ϳ40% of NK cells produced IFN-␥ at 36 h (47). No IFN-␥ production by NK cells was observed at 24 h, also consistent with previous studies (22).…”

Section: Ifn-i Inhibits MCMV Gene Expression In Mz Stromal Cells Higsupporting

confidence: 80%

Lymphoid-Tissue Stromal Cells Coordinate Innate Defense to Cytomegalovirus

Verma

Wang

Chodaczek

et al. 2013

J Virol

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bDuring mouse cytomegalovirus (MCMV) infection, the first wave of type I interferon (IFN-I) production peaks at ϳ8 h. This IFN-I emanates from splenic stromal cells located in the marginal zone (MZ) and requires B cells that express lymphotoxin. The amount of IFN-I produced at these initial times is at least equivalent in magnitude to that produced later by dendritic cells (ϳ36 to 48 h), but the relative roles of these two IFN-I sources in regulating MCMV defense remain unclear. Here we show that IFN-I produced by MZ stromal cells dramatically restricts the first measurable burst of viral production, which occurs at ϳ32 h. This primary innate control by IFN-I is partially mediated through the activation of natural killer (NK) cells, which produce gamma interferon in an IFN-I-dependent fashion, and is independent of Ly49H. Strikingly, MCMV production in the spleens of immunocompetent mice never increases at times after 32 h. These results highlight the critical importance of lymphoid-tissue stromal cells in orchestrating the earliest phase of innate defense to MCMV infection, capping replication levels, and blocking spread until infection is ultimately controlled.

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“…5A and B). As seen previously, ϳ40% of NK cells produced IFN-␥ at 36 h (47). No IFN-␥ production by NK cells was observed at 24 h, also consistent with previous studies (22).…”

Section: Ifn-i Inhibits MCMV Gene Expression In Mz Stromal Cells Higsupporting

confidence: 80%

Lymphoid-Tissue Stromal Cells Coordinate Innate Defense to Cytomegalovirus

Verma

Wang

Chodaczek

et al. 2013

J Virol

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“…Stimulation of CDP by TLRs induces chemokine CXC receptor (CXCR)4 downregulation and recruitment of pre-DCs to inflamed lymph nodes via chemokine CC receptor (CCR)7 [48]. Further DC development and particularly CD8 + DC development may be promoted in the spleen, due to the increased levels of FL that occur during microbial infections [53]. FL promotes both the BM and spleen stages of DC development, and is a limiting factor governing DC numbers [54].…”

Section: Reviewmentioning

confidence: 99%

Development of antigen cross-presentation capacity in dendritic cells

Dresch

Leverrier

Marvel

et al. 2012

Trends in Immunology

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“…In the absence of FLT3 signaling, pDCs are reduced in number in the lymphoid organs and bone marrow of mice 36,37 . FLT3L promotes pDC development through activation of signal transducer and activator of transcription 3 (STAT3)- and phosphoinositide 3-kinase (PI3K)-dependent activation of mammalian target of rapamycin (mTOR) 38,39 .…”

Section: Development Of Pdcsmentioning

confidence: 99%

The multifaceted biology of plasmacytoid dendritic cells

2015

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Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset that specializes in the production of type I interferons (IFNs). pDCs promote antiviral immune responses and have been implicated in the pathogenesis of autoimmune diseases characterized by a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. Here, we review recent progress from the field of pDC biology, focusing on: the molecular mechanisms that regulate pDC development and functions; the pathways involved in their sensing of pathogens and endogenous nucleic acids; the function of pDCs at mucosal sites; and their roles in infections, autoimmunity and cancer.

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Flt3 permits survival during infection by rendering dendritic cells competent to activate NK cells

Cited by 40 publications

References 30 publications

Lymphoid-Tissue Stromal Cells Coordinate Innate Defense to Cytomegalovirus

Lymphoid-Tissue Stromal Cells Coordinate Innate Defense to Cytomegalovirus

Development of antigen cross-presentation capacity in dendritic cells

The multifaceted biology of plasmacytoid dendritic cells

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