Neutrophils Transport Antigen from the Dermis to the Bone Marrow, Initiating a Source of Memory CD8+ T Cells

Duffy, Darragh; Perrin, Hélène; Abadie, Valérie; Benhabilès, Nora; Boissonnas, Alexandre; Liard, Christelle; Descours, Benjamin; Reboulleau, Damien; Bonduelle, Olivia; Verrier, Bernard; Rooijen, Nico van; Combadière, Christophe; Combadière, Béhazine

doi:10.1016/j.immuni.2012.07.015

Cited by 142 publications

(116 citation statements)

References 42 publications

(61 reference statements)

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“…For IL-8, an indicator for severity of inflammation and attractant of neutrophils, our qRT-PCR results indicate a barrier reconstitution after 24 h, which is coherent with our findings in skin physiology measurements for ex vivo probes [32,33]. IL-8 is a chemoattractant for neutrophils that also play a role in linking neutrophils to the adaptive immunity [34]. An increase is normally seen shortly after barrier perturbation as a sign of inflammation [15,16,35].…”

Section: Discussionsupporting

confidence: 84%

“…Interestingly, our early trials using CSSS for transcutaneous immunization also pointed towards systemic cytokine increase after influenza transcutaneous vaccination, e.g., IL-8 was elevated in transcutaneous vaccinated individuals [19]. An increase in expression of GM-CSF, a pro-inflammatory cytokine that enhances neutrophil and monocyte function, was observed indicating a role in early immune response [23,24,34,35]. The ex vivo qRT-PCR measurements showed a change in gene expression for IP-10 and TGF-β, both modulators that contribute to the induction of Langerhans cells and dendritic cell maturation as well as the positioning of CXCR3-positive T cells in the skin [16,23,24,36].…”

Section: Discussionmentioning

confidence: 99%

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Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption

Pfannes

Weiss²,

Hadam³

et al. 2018

Skin Pharmacol Physiol

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The success of topically applied treatments on skin relies on the efficacy of skin penetration. In order to increase particle or product penetration, mild skin barrier disruption methods can be used. We previously described cyanoacrylate skin surface stripping as an efficient method to open hair follicles, enhance particle penetration, and activate Langerhans cells. We conducted ex vivo and in vivo measurements on human skin to characterize the biological effect and quantify barrier disruption-related inflammation on a molecular level. Despite the known immunostimulatory effects, this barrier disruption and hair follicle opening method was well accepted and did not result in lasting changes of skin physiological parameters, cytokine production, or clinical side effects. Only in ex vivo human skin did we find a discrete increase in IP-10, TGF-β, IL-8, and GM-CSF mRNA. The data underline the safety profile of this method and demonstrate that the procedure per se does not cause substantial inflammation or skin damage, which is also of interest when applied to non-invasive sampling of biomarkers in clinical trials.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption

Pfannes

Weiss²,

Hadam³

et al. 2018

Skin Pharmacol Physiol

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“…This is not entirely unexpected, as CCR1 appears to be expressed on distinct subsets of T lymphocytes and is important for T cell migration to the lymph nodes (62). In addition CCR1 was also shown to play a role in an antigen transport mechanism whereby antigenloaded neutrophils migrate to the bone marrow, where a distinct subset of CD8 ϩ T cells is induced (10). In summary, we have demonstrated that CCR1 is important for MVA-triggered leukocyte migration in vivo, particularly with regard to neutrophil and inflammatory monocyte recruitment.…”

Section: Discussionmentioning

confidence: 86%

“…Systemic myxoma virus infection induces neutrophil recruitment to the liver microvasculature, where adherent neutrophils form large aggregates with platelets, releasing neutrophil extracellular traps that help to prevent infection of adjacent cells (9). Recent studies have indicated that the role of neutrophils during poxvirus infection may extend beyond direct antiviral activity, as during infection with modified vaccinia virus Ankara (MVA), neutrophils transport antigen from the dermis to the bone marrow, where a distinct subset of virus-specific CD8 ϩ T cells is induced (10). This reverse transmigration of neutrophils was mediated by chemokine (C-C motif) receptor 1 (CCR1), a chemokine receptor that seemingly fulfills a number of nonredundant functions in host defense (11).…”

mentioning

confidence: 99%

Chemokine (C-C Motif) Receptor 1 Is Required for Efficient Recruitment of Neutrophils during Respiratory Infection with Modified Vaccinia Virus Ankara

Price

Luckow

Torres-Domínguez

et al. 2014

J Virol

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Modified vaccinia virus Ankara (MVA) serves as a versatile platform in vaccine development. This highly attenuated orthopoxvirus, which cannot replicate in mammalian cells, triggers strong innate immune responses, including cell migration. Previously, we have shown that induction of chemokine (C-C motif) ligand 2 (CCL2) by MVA is necessary for the recruitment of monocytes and T cells, but not neutrophils, to the lung. Here, we identified neutrophil-attracting chemokines produced by MVA-infected primary murine lung fibroblasts and murine bone marrow-derived macrophages. We demonstrate that MVA, but not vaccinia virus (VACV) strain WR, induces chemokine expression, which is independent of Toll-like receptor 2 (TLR2) signaling. Additionally, we show that both chemokine (C-C motif) receptor 1 (CCR1) and chemokine (C-X-C motif) receptor 2 (CXCR2) are involved in MVA-induced neutrophil chemotaxis in vitro. Finally, intranasal infection of Ccr1 ؊/؊ mice with MVA, as well as application of the CCR1 antagonist J-113863, revealed a role for CCR1 in leukocyte recruitment, including neutrophils, into the lung.

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“…Distinct poxvirus vectors induce substantial differences in chemokine and cytokine profiles (21), which influence the adaptive immune responses. Whereas DCs and neutrophils transport VACV antigens to lymphoid organs and directly induce antigen-specific T cell responses (22,23), NK cells can generate the environment necessary to induce recruitment of activated T cells (20) or cross talk with DCs for the generation of antigen-specific T cell immunity (24).…”

mentioning

confidence: 99%

Distinct Roles of Vaccinia Virus NF-κB Inhibitor Proteins A52, B15, and K7 in the Immune Response

Pilato

Mejías-Pérez

Sorzano

et al. 2017

J Virol

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Poxviruses use a complex strategy to escape immune control, by expressing immunomodulatory proteins that could limit their use as vaccine vectors. To test the role of poxvirus NF-B pathway inhibitors A52, B15, and K7 in immunity, we deleted their genes in an NYVAC (New York vaccinia virus) strain that expresses HIV-1 clade C antigens. After infection of mice, ablation of the A52R, B15R, and K7R genes increased dendritic cell, natural killer cell, and neutrophil migration as well as chemokine/cytokine expression. Revertant viruses with these genes confirmed their role in inhibiting the innate immune system. To different extents, enhanced innate immune responses correlated with increased HIV Pol-and Gag-specific polyfunctional CD8 T cell and HIV Env-specific IgG responses induced by single-, double-, and triple-deletion mutants. These poxvirus proteins thus influence innate and adaptive cell-mediated and humoral immunity, and their ablation offers alternatives for design of vaccine vectors that regulate immune responses distinctly.IMPORTANCE Poxvirus vectors are used in clinical trials as candidate vaccines for several pathogens, yet how these vectors influence the immune system is unknown. We developed distinct poxvirus vectors that express heterologous antigens but lack different inhibitors of the central host-cell signaling pathway. Using mice, we studied the capacity of these viruses to induce innate and adaptive immune responses and showed that these vectors can distinctly regulate the magnitude and quality of these responses. These findings provide important insights into the mechanism of poxvirus-induced immune response and alternative strategies for vaccine vector design.KEYWORDS NF-B, NYVAC, T cell immunity, adaptive immunity, human immunodeficiency virus, immunomodulation, innate immunity, poxvirus, vaccines, vaccinia virus S everal vaccine strategies have been developed to improve immune responses to heterologous antigens expressed by attenuated poxvirus vectors (1). Given the limited effectiveness of the ALVAC poxvirus vector in the RV144 phase III HIV/AIDS clinical trial (2), the need remains to improve poxvirus vector capacity as an immunogen, to increase protection levels, and to understand how innate and adaptive immune responses can be regulated.The attenuated poxvirus strain NYVAC (New York vaccinia virus) has been used as a vaccine vector in HIV clinical trials (3,4). Studies in nonhuman primates showed that NYVAC expressing Env and/or the Gag-Pol-Nef (GPN) clade C HIV antigens elicited a balanced CD4/CD8 T cell response (5) or robust T cell immunity (6). In clinical trials in healthy volunteers and in chronically HIV-infected patients, NYVAC showed clear immunogenic potential to induce expansion of preexisting T cell responses as well as the appearance of newly detected polyfunctional CD8 T cell responses (7).

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Neutrophils Transport Antigen from the Dermis to the Bone Marrow, Initiating a Source of Memory CD8+ T Cells

Cited by 142 publications

References 42 publications

Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption

Physiological and Molecular Effects of in vivo and ex vivo Mild Skin Barrier Disruption

Chemokine (C-C Motif) Receptor 1 Is Required for Efficient Recruitment of Neutrophils during Respiratory Infection with Modified Vaccinia Virus Ankara

Distinct Roles of Vaccinia Virus NF-κB Inhibitor Proteins A52, B15, and K7 in the Immune Response

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