Porcine CD8αdim/-NKp46high NK cells are in a highly activated state

Mair, Kerstin H.; Müllebner, Andrea; Essler, Sabine E.; Duvigneau, J.C.; Storset, Anne K.; Saalmüller, Armin; Gerner, Wilhelm

doi:10.1186/1297-9716-44-13

Cited by 38 publications

(60 citation statements)

References 55 publications

(91 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This population was also found in liver and spleen in the current study (data not shown) and has been described earlier [22]. Increased expression of NKp46 has been linked to activation of NK cells in both swine and humans [23], [45] and in line with this, a higher percentage of the lung NKp46 high cells in this study expressed the activation marker CD25 compared to NKp46 − and NKp46 int NK cells. A higher expression of CD27 has also been found on this population in spleen [23].…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

Early Responses of Natural Killer Cells in Pigs Experimentally Infected with 2009 Pandemic H1N1 Influenza A Virus

et al. 2014

Self Cite

View full text Add to dashboard Cite

Natural killer (NK) cells are important players in the innate immune response against influenza A virus and the activating receptor NKp46, which binds hemagglutinin on the surface of infected cells, has been assigned a role in this context. As pigs are natural hosts for influenza A viruses and pigs possess both NKp46− and NKp46+ NK cells, they represent a good animal model for studying the role of the NKp46 receptor during influenza. We explored the role of NK cells in piglets experimentally infected with 2009 pandemic H1N1 influenza virus by flow cytometric analyses of cells isolated from blood and lung tissue and by immunostaining of lung tissue sections. The number of NKp46+ NK cells was reduced while NKp46− NK cells remained unaltered in the blood 1–3 days after infection. In the lungs, the intensity of NKp46 expression on NK cells was increased during the first 3 days, and areas where influenza virus nucleoprotein was detected were associated with increased numbers of NKp46+ NK cells when compared to uninfected areas. NKp46+ NK cells in the lung were neither found to be infected with influenza virus nor to be undergoing apoptosis. The binding of porcine NKp46 to influenza virus infected cells was verified in an in vitro assay. These data support the involvement of porcine NKp46+ NK cells in the local immune response against influenza virus.

show abstract

Section: Discussionsupporting

confidence: 91%

“…In liver and spleen, a third NK cell population with a higher NKp46 expression and a dim or negative CD8α expression has been described [22]. These CD8 −/dim NKp46 high NK cells appear to represent a more activated state [23].…”

Section: Introductionmentioning

confidence: 99%

Early Responses of Natural Killer Cells in Pigs Experimentally Infected with 2009 Pandemic H1N1 Influenza A Virus

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Next to T and B cells NK cells were addressed as another major lymphocyte subset, including NKp46-defined subsets which have been investigated in pigs previously [31, 32]. Absolute numbers of NK cells and NKp46 + NK cells in blood were slightly enhanced in E. coli O157:H7 infected animals and even more in E. coli O104:H4 infected animals (Fig.…”

Section: Resultsmentioning

confidence: 99%

Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7

et al. 2017

Self Cite

View full text Add to dashboard Cite

BackgroundShiga toxin (Stx) producing Escherichia coli (E. coli) (STEC) is the most frequent cause of diarrhoea-positive haemolytic uraemic syndrome (D + HUS) in humans. In 2011, a huge outbreak with an STEC O104:H4 strain in Germany highlighted the limited possibilities for causative treatment of this syndrome. The responsible STEC strain was found to combine Stx production with adherence mechanisms normally found in enteroaggregative E. coli (EAEC). Pathotypes of E. coli evolve and can exhibit different adhesion mechanisms. It has been shown previously that neonatal gnotobiotic piglets are susceptible for infection with STEC, such as STEC O157:H7 as well as for EAEC, which are considered to be the phylogenetic origin of E. coli O104:H4. This study was designed to characterise the host response to infection with the STEC O104:H4 outbreak strain in comparison to an STEC O157:H7 isolate by evaluating clinical parameters (scoring) and markers of organ dysfunction (biochemistry), as well as immunological (flow cytometry, assessment of cytokines/chemokines and acute phase proteins) and histological alterations (light- and electron microscopy) in a gnotobiotic piglet model of haemolytic uraemic syndrome.ResultsWe observed severe clinical symptoms, such as diarrhoea, dehydration and neurological disorders as well as attaching-and-effacing lesions (A/E) in the colon in STEC O157:H7 infected piglets. In contrast, STEC O104:H4 challenged animals exhibited only mild clinical symptoms including diarrhoea and dehydration and HUS-specific/severe histopathological, haematological and biochemical alterations were only inconsistently presented by individual piglets. A specific adherence phenotype of STEC O104:H4 could not be observed. Flow cytometric analyses of lymphocytes derived from infected animals revealed an increase of natural killer cells (NK cells) during the course of infection revealing a potential role of this subset in the anti-bacterial activity in STEC disease.ConclusionsUnexpectedly, E. coli O104:H4 infection caused only mild symptoms and minor changes in histology and blood parameters in piglets. Outcome of the infection trial does not reflect E. coli O104:H4 associated human disease as observed during the outbreak in 2011. The potential role of cells of the innate immune system for STEC related disease pathogenesis should be further elucidated.

show abstract

“…Human NK cells were isolated from peripheral blood mononuclear cells (PBMC) using the RosetteSepTM NK Cell Enrichment kit (Stemcell Technologies), cultured in the presence of 100 units/mL huIL2 (Chiron) as described before (47) and used within 3 wk. Primary porcine NK cells were isolated from porcine PBMC by negative MACS depletion and a FACS purification step using antibodies against porcine CD172, CD3, CD4, and CD8α, essentially as described before (48,49) and primed for 18 h with 40 units/mL recombinant huIL2 (Invitrogen). CD16 expression on sorted cells confirmed ≥98% NK purity.…”

Section: Methodsmentioning

confidence: 99%

Modulation of CD112 by the alphaherpesvirus gD protein suppresses DNAM-1–dependent NK cell-mediated lysis of infected cells

Grauwet

Cantoni

Parodi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance Herpesviruses have developed fascinating mechanisms to evade elimination by key elements of the host immune system, allowing these pathogens to cause lifelong infections with periods of recurrent virus spread. Natural killer (NK) cells are central in the innate antiviral response. Here, we report that the gD glycoprotein of the alphaherpesviruses, pseudorabies virus and herpes simplex virus-2, displays previously uncharacterized immune evasion properties toward NK cells. Expression of the gD protein leads to degradation of CD112/nectin-2, a ligand for the NK-activating receptor DNAX accessory molecule 1 (DNAM-1). This impairs binding of DNAM-1 to the cell surface, thereby suppressing NK-mediated killing of virus-infected (or gD-transfected) cells. Identification of this previously unidentified immune evasion mechanism may contribute to the design of improved herpesvirus vaccines and herpesvirus-based therapeutic vectors.

show abstract

Porcine CD8αdim/-NKp46high NK cells are in a highly activated state

Cited by 38 publications

References 55 publications

Early Responses of Natural Killer Cells in Pigs Experimentally Infected with 2009 Pandemic H1N1 Influenza A Virus

Early Responses of Natural Killer Cells in Pigs Experimentally Infected with 2009 Pandemic H1N1 Influenza A Virus

Comparison of clinical and immunological findings in gnotobiotic piglets infected with Escherichia coli O104:H4 outbreak strain and EHEC O157:H7

Modulation of CD112 by the alphaherpesvirus gD protein suppresses DNAM-1–dependent NK cell-mediated lysis of infected cells

Contact Info

Product

Resources

About