Dynamics of Neutrophil Migration in Lymph Nodes during Infection

Chtanova, Tatyana; Schaeffer, Marie; Han, Seong-Ji; Dooren, Giel G. van; Nollmann, Marcelo; Herzmark, Paul; Chan, Shiao Wei; Satija, Harshita; Camfield, Kristin A; Aaron, Holly L.; Striepen, Boris; Robey, Ellen

doi:10.1016/j.immuni.2008.07.012

Cited by 355 publications

(282 citation statements)

References 43 publications

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“…A46 and C49 are other NYVAC NF-B inhibitors (35, 36) whose contribution to induction of innate immune responses might be better determined by removing these We show that A52 is partially involved in DC evasion and suggest that DCs recruited after infection are involved in HIV-specific CD8 T cell and IgG responses. Neutrophils cross-prime naive T cells and induce adaptive immune responses (40,41). A52R, B15R, and K7R gene deletion enhances chemokines that can directly induce neutrophil migration, and thus HIV-specific CD8 T cell and IgG responses, which supports neutrophil mediation of HIV immune responses (18).…”

Section: Discussionmentioning

confidence: 92%

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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Section: Discussionmentioning

confidence: 92%

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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“…Earlier studies indicated that neutrophils were able to present exogenous antigen to CD8+ T-cells [7] and recent data have shown also antigen-presentation to Th1 and Th17 cells [2]. In confocal microscopic studies neutrophils migrating with fluorescently labeled pathogen were observed in draining lymph vessels [1] and lymph nodes [21]. Moreover, the chemokine receptor CCR7 has been identified as a key player in directing neutrophil migration from the interstitium to the draining lymph nodes [6].…”

Section: Interaction With Other Immune Cellsmentioning

confidence: 96%

Changing world of neutrophils

Tímár

Lörincz

Ligeti

2013

Pflugers Arch - Eur J Physiol

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“…Cell attachment to substrate per se may participate to the increase of immune activity and respiratory burst. In mammals, immune cells are known to migrate rapidly towards the site of infection (Abadie et al 2005;Chtanova et al 2008;Germain et al 2012). Interestingly, ex vivo explant experiments give evidence for accelerated random migration of immune cells, at rates of 8 lm min -1 , similar to interstitial velocities reported for neutrophils at sites of inflammation (Graham et al 2009;Kreisel et al 2010).…”

Section: Discussionmentioning

confidence: 68%

Cell tracking and velocimetric parameters analysis as an approach to assess activity of mussel (Mytilus edulis) hemocytes in vitro

Rioult

Lebel²,

Foll

2013

Cytotechnology

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Hemocytes constitute the key element of innate immunity in bivalves, being responsible for secretion of antimicrobial peptides and release of zymogens from the prophenoloxidase system within the hemolymph compartment, reactive oxygen species production and phagocytosis. Hemocytes are found (and collected) as cells in suspension in circulating hemolymph. Hemocytes are adherent cells as well, infiltrating tissues and migrating to infected areas. In the present study, we applied an approach based on fluorescent staining and nuclei-tracking to determine migration velocity of hemocytes from the blue mussel, Mytilus edulis, in culture. Freshly collected hemocytes attached to substrate and start to move spontaneously in few minutes. Two main hemocyte morphologies can be observed: small star-shaped cells which were less motile and spread granular cells with faster migrations. Cell-tracking was combined to MTT mitochondria metabolic rate measurements in order to monitor global cell population activity over 4 days of culture. A transient peak of cell activity was recorded after 24-48 h of culture, corresponding to a speed up of cell migration. Videomicroscopy and cell tracking techniques provide new tools to characterize activity of mussel immunocytes in culture. Our analysis of hemocyte migration reveals that motility is very sensitive to cell environmental factors.

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Dynamics of Neutrophil Migration in Lymph Nodes during Infection

Cited by 355 publications

References 43 publications

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

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

Changing world of neutrophils

Cell tracking and velocimetric parameters analysis as an approach to assess activity of mussel (Mytilus edulis) hemocytes in vitro

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