γδ T cells mediate a requisite portion of a wound healing response triggered by cutaneous poxvirus infection DOI Creative Commons
Irene E. Reider, Eugene Lin,

Tracy E. Krouse

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: Sept. 1, 2020

Abstract Infection at peripheral sites, such as the skin, activates local innate immune defenses tasked with limiting spread of pathogen while preserving tissue integrity. T cells bearing γδ Cell Receptors (TCR), which comprise multiple phenotypically distinct subtypes cells, reside in normal where they shape immunity to cutaneous infection, prior onset an adaptive response by conventional αβ CD4 + (T CD4+ ) and CD8 CD8+ cells. The mechanisms used control virus replication pathology following infection are unknown, so we examined role vaccinia (VACV). Resident skin expanded combined recruited observed after VACV infection. However, no defect or increased systemic mice lacking despite induction a cytolytic specialized subset resident While examining cell-mediated identified unique wound healing signature associated that has features common to, but also antagonize, sterile response. Typically, repair is thought occur only clearance pathogen, viral was evident peak skin. contributed this through cytokines growth factors required for efficient closure. Therefore, early mediators likely important maintenance barrier function prevention secondary bacterial Author Summary among first cell types positioned be able respond it assumed these play similar their widespread throughout body, namely kill infected slow spread. found Rather, functioned critical component previously unrecognized started occurs same time aims clear virus. This study describe both response, information could allow manipulation decrease change scarring infections.

Language: Английский

Molecular mechanisms of regulation of Toll-like receptor signaling DOI
Cynthia A. Leifer, Andrei E. Medvedev

Journal of Leukocyte Biology, Journal Year: 2016, Volume and Issue: 100(5), P. 927 - 941

Published: June 24, 2016

Abstract TLRs play a critical role in the detection of microbes and endogenous “alarmins” to initiate host defense, yet they can also contribute development progression inflammatory autoimmune diseases. To avoid pathogenic inflammation, TLR signaling is subject multilayer regulatory control mechanisms, including cooperation with coreceptors, post-translational modifications, cleavage, cellular trafficking, interactions negative regulators. Nucleic acid-sensing are particularly interesting this regard, as both recognize host-derived structures require internalization their ligand result intracellular sequestration nucleic TLRs. This review summarizes mechanisms TLRs, regulation access ligands, receptor folding, well how altered mechanism could disorders.

Language: Английский

Citations

229
Poxviruses and the immune system: Implications for monkeypox virus DOI Open Access
Amene Saghazadeh,

Nima Rezaei

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 113, P. 109364 - 109364

Published: Oct. 22, 2022

Language: Английский

Citations

39
Innate Immune Response to MPOX Infection: Mechanisms and Immune Escape DOI Creative Commons

Reza Parnian,

Fatemeh Heydarifard,

F Mousavi

et al.

Journal of Innate Immunity, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 13, 2024

The re-emergence of the Mpox (formerly monkeypox) in 2022 non-endemic countries has raised many concerns for global health due to its high transmissibility and mortality rate. A major challenge fighting is ability evade host's innate immune system, which first line defense against viral infections. encodes various proteins that interfere with key antiviral pathways mechanisms, such as nuclear factor kappa B (NF-κB) signaling, cytokine production, complement inflammasome activation, chemokine binding. These modulate expression function mediators, interferons, interleukins, toll-like receptors, impair recruitment activation cells, natural killer cells. By suppressing or altering these responses, enhances replication infection host tissues organs, leading systemic inflammation, tissue damage, organ failure. This study reveals new insights into molecular cellular interactions between host’s immunity identifies potential targets strategies interventions.

Language: Английский

Citations

6
Innate immune activation of NFκB and its antagonism by poxviruses DOI
Gareth Brady, Andrew Bowie

Cytokine & Growth Factor Reviews, Journal Year: 2014, Volume and Issue: 25(5), P. 611 - 620

Published: July 11, 2014

Language: Английский

Citations

47
Danger, diversity and priming in innate antiviral immunity DOI
Susan E. Collins, Karen L. Mossman

Cytokine & Growth Factor Reviews, Journal Year: 2014, Volume and Issue: 25(5), P. 525 - 531

Published: July 11, 2014

Language: Английский

Citations

45
A systemic macrophage response is required to contain a peripheral poxvirus infection DOI Creative Commons
Michael L. Davies, Nikhil J. Parekh, Lauren W. Kaminsky

et al.

PLoS Pathogens, Journal Year: 2017, Volume and Issue: 13(6), P. e1006435 - e1006435

Published: June 14, 2017

The goal of the innate immune system is to reduce pathogen spread prior initiation an effective adaptive response. Following infection at a peripheral site, virus typically drains through lymph node entering blood stream and being systemically disseminated. Therefore, there are three distinct spatial checkpoints which intervention prevent systemic can occur, namely: 1) site infection, 2) draining via filtration or 3) level organs that filter blood. We have previously shown depletion phagocytic cells allows viral after dermal with Vaccinia (VACV), infects naturally skin. Here we use multiple methodologies define both checkpoint identity VACV. Subcapsular sinus macrophages been implicated as critical effectors in clearance borne viruses following infection. find monocyte populations recruited VACV play role control local pathogenesis tissue damage, but do not dissemination virus. virulent VACV, subcapsular within become infected, exclusively required spread. Rather, small doses enter bloodstream function macrophages, dendritic cells, further results illustrate response may be widespread pathology viruses, such poxviruses.

Language: Английский

Citations

27
Type I interferon-dependent CCL4 is induced by a cGAS/STING pathway that bypasses viral inhibition and protects infected tissue, independent of viral burden DOI Creative Commons
Nikhil J. Parekh,

Tracy E. Krouse,

Irene E. Reider

et al.

PLoS Pathogens, Journal Year: 2019, Volume and Issue: 15(10), P. e1007778 - e1007778

Published: Oct. 11, 2019

Type I interferons (T1-IFN) are critical in the innate immune response, acting upon infected and uninfected cells to initiate an antiviral state by expressing genes that inhibit multiple stages of lifecycle many viruses. T1-IFN triggers production Interferon-Stimulated Genes (ISGs), activating program reduces virus replication. The importance response is highlighted evolution viral evasion strategies or action virus-infected cells. produced via activation pathogen sensors within cells, a process targeted virus-encoded immunomodulatory molecules. This probably best exemplified prototypic poxvirus, Vaccinia (VACV), which uses at least 6 different mechanisms completely block vitro. Yet, mice lacking aspects signaling often more susceptible infection with viruses, including VACV, than wild-type mice. How can these opposing findings be rationalized? cytosolic DNA sensor cGAS has been implicated immunity but yet linked VACV infection. Indeed, there two VACV-encoded proteins effectively prevent cGAS-mediated T1-IFN. We find majority VACV-infected vivo do not produce T1-IFN, small subset utilize sense protect protective effect mediated ISG-mediated control Rather, drives increased expression CCL4, recruits inflammatory monocytes constrain lesion replication-independent manner limiting spread tissue. Our have broad implications our understanding detection vivo, highlight novel strategy

Language: Английский

Citations

23
Myeloid Cell-Mediated Trained Innate Immunity in Mucosal AIDS Vaccine Development DOI Creative Commons
Yongjun Sui, Jay A. Berzofsky

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Feb. 28, 2020

Trained innate immunity has recently emerged as a novel concept of immune cells, such myeloid exhibiting memory and nonspecific heterologous to protect against infections. The specificity are mediated by epigenetic, metabolic, functional reprogramming the cells progenitors (and/or NK cells) in bone marrow peripheral tissues gut lung mucosa. A variety agents, BCG, viruses, their components, well TLR agonists, cytokines have been shown be involved induction trained immunity. Since these agents widely used AIDS vaccine development antigen delivery vectors or adjuvants, cell might also play an important role protecting mucosal virus transmission control replication major reservoir. Here we review induced vectors/adjuvants that studies discuss efficacy possible utilization development. Delineating protective effect will guide design vaccines.

Language: Английский

Citations

22
Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures DOI Creative Commons
Jessamine E. Hazlewood, Troy Dumenil, Thuy T. Le

et al.

PLoS Pathogens, Journal Year: 2021, Volume and Issue: 17(1), P. e1009215 - e1009215

Published: Jan. 13, 2021

Poxvirus systems have been extensively used as vaccine vectors. Herein a RNA-Seq analysis of intramuscular injection sites provided detailed insights into host innate immune responses, well expression vector and recombinant immunogen genes, after vaccination with new multiplication defective, vaccinia-based vector, Sementis Copenhagen Vector. Chikungunya Zika virus mRNA protein was associated necrosing skeletal muscle cells surrounded by mixed cellular infiltrates. The multiple adjuvant signatures at 12 hours post-vaccination were dominated TLR3, 4 9, STING, MAVS, PKR the inflammasome. Th1 cytokine IFNγ, TNF IL1β, chemokine CCL5 CXCL12. Multiple dendritic cell stimulation evident. By day seven, transcripts absent, death, neutrophil, macrophage inflammation annotations had abated. No compelling arthritis identified. Such site vaccinology approaches should inform refinements in poxvirus-based design.

Language: Английский

Citations

17
γδ T Cells Mediate a Requisite Portion of a Wound Healing Response Triggered by Cutaneous Poxvirus Infection DOI Creative Commons
Irene E. Reider, Eugene Lin,

Tracy E. Krouse

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(3), P. 425 - 425

Published: March 10, 2024

Infection at barrier sites, e.g., skin, activates local immune defenses that limit pathogen spread, while preserving tissue integrity. Phenotypically distinct γδ T cell populations reside in where they shape immunity to cutaneous infection prior onset of an adaptive response by conventional αβ CD4+ (TCD4+) and CD8+ (TCD8+) cells. To examine the mechanisms used cells control virus replication pathology, we examined after with vaccinia (VACV). Resident expanded combined recruited pathology VACV infection. However, did not play a role or blockade systemic spread. We identified unique wound healing signature has features common to, but also antagonize, sterile response. Tissue repair generally occurs clearance pathogen, viral started peak skin. contributed through induction multiple cytokines/growth factors required for efficient closure. Therefore, modulate following infection, maintaining skin function prevent secondary bacterial

Language: Английский

Citations

2