Deciphering the role of DC subsets in MCMV infection to better understand immune protection against viral infections

Alexandre, Yannick O.; Cocita, ClÃ©ment D.; Ghilas, Sonia; Dalod, Marc

doi:10.3389/fmicb.2014.00378

Cited by 49 publications

(55 citation statements)

References 141 publications

(241 reference statements)

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“…Because macrophages, conventional dendritic cells (cDC), and plasmacytoid dendritic cells (pDC) have all been described to produce IL-12 in vivo during pathogen challenge (Alexandre et al, 2014; Trinchieri, 2003), we utilized Il-12p40 -YFP reporter mice to determine the major cellular source of local IL-12 in virally infected tissues. Unbiased analysis of total YFP + cells revealed that the majority of IL-12 producing cells at 12 hours PI in the PC and liver, or at 36 hours PI in the lung, respectively, were CD64 − CD11c hi MHCII hi CD11b − XCR1 + cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

ILC1 Confer Early Host Protection at Initial Sites of Viral Infection

Weizman

Adams

Schuster

et al. 2017

Cell

367

456

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Summary Infection is restrained by the concerted activation of tissue-resident and circulating immune cells. Whether tissue-resident lymphocytes confer early antiviral immunity at local sites of primary infection prior to the initiation of circulating responses is not well understood. Furthermore, the kinetics of initial antiviral responses at sites of infection remain unclear. Here, we show that tissue-resident type 1 innate lymphoid cells (ILC1) serve an essential early role in host immunity through rapid production of interferon (IFN)-γ following viral infection. Ablation of Zfp683-dependent liver ILC1 lead to increased viral load in the presence of intact adaptive and innate immune cells critical for mouse cytomegalovirus (MCMV) clearance. Swift production of IL-12 by tissue-resident XCR1+ conventional dendritic cells (cDC1) promoted ILC1 production of IFN-γ in a STAT4-dependent manner to limit early viral burden. Thus, ILC1 contribute an essential role in viral immunosurveillance at sites of initial infection in response to local cDC1-derived proinflammatory cytokines.

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Section: Resultsmentioning

confidence: 99%

ILC1 Confer Early Host Protection at Initial Sites of Viral Infection

Weizman

Adams

Schuster

et al. 2017

Cell

367

456

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“…DC are heterogeneous mononuclear phagocytes which can be classified in different subsets due to their ontogeny, surface markers, and functions (24). Murine plasmacytoid DC (pDC) are described as CD11b Ϫ CD11c int SiglecH ϩ and are the major source of interferon alpha/beta (IFN-␣/␤) in response to MCMV infection (25)(26)(27).…”

mentioning

confidence: 99%

“…However, all of these studies were performed with monocultures of DC infected at a high multiplicity of infection (MOI), which might not reflect the in vivo situation, where most of the infected cells are epithelial and endothelial cells, which show higher permissiveness for MCMV than DC. Hence, it is still unclear if DC restrict or contribute to viral replication and spread (24).…”

mentioning

confidence: 99%

Type I Interferon Released by Myeloid Dendritic Cells Reversibly Impairs Cytomegalovirus Replication by Inhibiting Immediate Early Gene Expression

Holzki

Dağ

Dekhtiarenko

et al. 2015

J Virol

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Cytomegalovirus (CMV) is a ubiquitous beta-herpesvirus whose reactivation from latency is a major cause of morbidity and mortality in immunocompromised hosts. Mouse CMV (MCMV) is a well-established model virus to study virus-host interactions. We showed in this study that the CD8-independent antiviral function of myeloid dendritic cells (mDC) is biologically relevant for the inhibition of MCMV replication in vivo and in vitro. In vivo ablation of CD11c ؉ DC resulted in higher viral titers and increased susceptibility to MCMV infection in the first 3 days postinfection. We developed in vitro coculture systems in which we cocultivated MCMV-infected endothelial cells or fibroblasts with T cell subsets and/or dendritic cells. H uman cytomegalovirus (HCMV) is a betaherpesvirus which establishes a lifelong latent infection in immunocompetenthosts. Latent HCMV is present in the majority of people worldwide, but the primary infection is usually asymptomatic. The primary infection is well contained by the immune cells, such as natural killer (NK) cells and T cells, which also prevent viral reactivation from latency (1, 2).Their activation depends on cross talk with dendritic cells (DC) (3, 4), and this interaction plays an important role in CMV control (5-7). The direct effect of DC on viral replication remains, however, unclear.In immunocompromised hosts, like AIDS patients or people undergoing transplantation, the virus cannot be contained, and its reactivation from latency has been associated with severe disease (8). Therefore, to develop new therapeutic approaches against CMV disease, it is exceedingly important to understand the immune mechanisms that drive the virus into latency.Murine cytomegalovirus (MCMV) is a natural pathogen of the mouse. It shows numerous analogies in latency and reactivation to the human virus, and its genome displays substantial similarity to the HCMV one (9). Therefore, MCMV is a widely used model for CMV infection and immunity (10)(11)(12).During primary infection, MCMV infects various different cell types, such as macrophages and DC but also nonhematopoietic cells, including endothelial and epithelial cells (13). On the other hand, the establishment of latency appears to be restricted to certain cell types. Latent HCMV was found in blood monocytes and in progenitor cells of the myeloid lineage (14-19), whereas liver sinusoidal endothelial cells (LSEC) were shown to be a site of MCMV latency and reactivation (20, 21), although myeloid cells might also present a latent reservoir in the mouse (22, 23).

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“…TLR‐dependent plasmacytoid dendritic cells (pDCs) are thought to be the primary cellular source of type 1 IFNs, although there are recent reports that the earliest type 1 IFN production following CMV is mediated by cGAS‐STING signaling in non‐hematopoietic cells, monocyte‐derived DCs, and macrophages . pDCs have also been described to produce IL‐12 during pathogen challenge . However, a recent study, using an unbiased analysis of YFP + cells from Il‐12p40 ‐YFP reporter mice, identified XCR1 + conventional dendritic cells (cDC1s) as the major early producers of IL‐12 in infected tissues following MCMV infection .…”

Section: Waves Of Antiviral Immunitymentioning

confidence: 99%

Spatial and temporal coordination of antiviral responses by group 1 ILCs

Adams

Sun

2018

Immunological Reviews

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Summary Group 1 innate lymphocytes consist of a phenotypically, spatially, and functionally heterogeneous population of NK cells and ILC1s that are engaged during pathogen invasion. We are only beginning to understand the context-dependent roles that different subsets of group 1 innate lymphocytes play during homeostatic perturbations. With a focus on viral infection, this review highlights the organization and regulation of spatially and temporally distinct waves of NK cell and ILC1 responses that collectively serve to achieve optimal viral control.

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Deciphering the role of DC subsets in MCMV infection to better understand immune protection against viral infections

Cited by 49 publications

References 141 publications

ILC1 Confer Early Host Protection at Initial Sites of Viral Infection

ILC1 Confer Early Host Protection at Initial Sites of Viral Infection

Type I Interferon Released by Myeloid Dendritic Cells Reversibly Impairs Cytomegalovirus Replication by Inhibiting Immediate Early Gene Expression

Spatial and temporal coordination of antiviral responses by group 1 ILCs

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