Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Jans, Jop; Unger, Wendy W.J.; Vissers, Marloes; Ahout, Inge M. L.; Schreurs, Inge; Wickenhagen, Arthur; Groot, Ronald de; Jonge, Marien I. de; Ferwerda, Gerben

doi:10.1002/eji.201747161

Cited by 23 publications

(25 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…mCD169 seems to be a general biomarker of acute viral infections since it has been found in patients with HIV (16, 18,19), EBV (20), RSV (21), CMV (22), Dengue (23,24), Zika (25), noroviruses (26), Lassa and Marburg (27). Here, high levels of mCD169 have been observed for the first time for Flu A virus.…”

Section: Discussionmentioning

confidence: 66%

CD64 and CD169 could help differentiate bacterial from viral infections in Emergency Department

Bourgoin

Soliveres²,

Barbaresi³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The identification of a bacterial, viral or even non-infectious cause is essential in the management of febrile syndrome in the emergency department (ED) setting, especially in epidemic contexts such as flu or CoVID-19. Objectives: The aim of this study was to assess discriminative performances of two biomarkers, CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169), using a new flow cytometry procedure, in patients presenting with fever to the ED. Human leucocyte antigen-DR on monocytes (mHLA-DR), HLA-ABC ratio (rHLA-ABC), and CD64 on monocytes (mCD64) were also assessed. Methods: 85 adult patients presenting with potential infection were included during the 2019 flu season in the ED of La Timone Hospital. They were divided into four diagnostic outcomes according to their clinical records: no-infection, bacterial infection, viral infection and co-infection. Results: mCD169 was elevated in patients suffering from Flu A virus or Respiratory Syncytial Virus, while nCD64 was mainly found elevated in subjects with Streptococcus pneumoniae. In total, 38 (45%) patients were diagnosed with bacterial infections, 11 (13%) with viral infections and 29 (34%) with co-infections. nCD64 and mCD169 showed 90% and 80% sensitivity, and 78% and 91% specificity, respectively, for identifying patients with bacterial or viral infections. Other biomarkers had lower discriminative performances. Conclusions: nCD64 and mCD169 have potential for accurately distinguishing bacterial and acute viral infections. Combined in an easy and rapid flow cytometry procedure, they constitute a potential improvement for infection management in the ED setting, and could even help for the triage of patients during emerging epidemics.

show abstract

Section: Discussionmentioning

confidence: 66%

CD64 and CD169 could help differentiate bacterial from viral infections in Emergency Department

Bourgoin

Soliveres²,

Barbaresi³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The gene most highly induced in response to HuNoV infection in both organoid lines was the IFI44L gene, encoding a novel tumor suppressor (64) previously show to have modest antiviral activity against hepatitis C virus (HCV) (65) and respiratory syncytial virus (RSV) (66,67). IFI44L was also potently upregulated in IECs infected with human rotavirus (HRV) (68).…”

Section: Discussionmentioning

confidence: 99%

Norovirus Replication in Human Intestinal Epithelial Cells Is Restricted by the Interferon-Induced JAK/STAT Signaling Pathway and RNA Polymerase II-Mediated Transcriptional Responses

Hosmillo

Chaudhry

Nayak

et al. 2020

mBio

View full text Add to dashboard Cite

Human noroviruses (HuNoV) are a leading cause of viral gastroenteritis worldwide and a significant cause of morbidity and mortality in all age groups. The recent finding that HuNoV can be propagated in B cells and mucosa-derived intestinal epithelial organoids (IEOs) has transformed our ability to dissect the life cycle of noroviruses. Using transcriptome sequencing (RNA-Seq) of HuNoV-infected intestinal epithelial cells (IECs), we have found that replication of HuNoV in IECs results in interferon (IFN)-induced transcriptional responses and that HuNoV replication in IECs is sensitive to IFN. This contrasts with previous studies that suggested that the innate immune response may play no role in the restriction of HuNoV replication in immortalized cells. We demonstrated that inhibition of Janus kinase 1 (JAK1)/JAK2 enhanced HuNoV replication in IECs. Surprisingly, targeted inhibition of cellular RNA polymerase II-mediated transcription was not detrimental to HuNoV replication but instead enhanced replication to a greater degree than blocking of JAK signaling directly. Furthermore, we demonstrated for the first time that IECs generated from genetically modified intestinal organoids, engineered to be deficient in the interferon response, were more permissive to HuNoV infection. Taking the results together, our work revealed that IFN-induced transcriptional responses restrict HuNoV replication in IECs and demonstrated that inhibition of these responses mediated by modifications of the culture conditions can greatly enhance the robustness of the norovirus culture system. IMPORTANCE Noroviruses are a major cause of gastroenteritis worldwide, and yet the challenges associated with their growth in culture have greatly hampered the development of therapeutic approaches and have limited our understanding of the cellular pathways that control infection. Here, we show that human intestinal epithelial cells, which represent the first point of entry of human noroviruses into the host, limit virus replication by induction of innate responses. Furthermore, we show that modulating the ability of intestinal epithelial cells to induce transcriptional responses to HuNoV infection can significantly enhance human norovirus replication in culture. Collectively, our findings provide new insights into the biological pathways that control norovirus infection but also identify mechanisms that enhance the robustness of norovirus culture.

show abstract

“…Finally, Siglec-1 modulates T cell-mediated anti-viral responses during human respiratory syncytial virus (RSV) infection, with key differences between newborns and adults. Upon RSV infection, expression of Siglec-1 is upregulated on monocytes from both newborns and adults, whereas expression of Siglec-1 ligand, CD43, is only highly upregulated on adult CD4 + T cells (van den Berg et al 2001;Jans et al 2018). This finding is consistent with observations that Siglec-1 inhibits IFN-γ production by adult CD4 + T cells but not newborn CD4 + T cells, although the detailed mechanism remains unknown (Jans et al 2018).…”

Section: Siglecs In Viral Infectionmentioning

confidence: 99%

Siglecs at the Host–Pathogen Interface

Chang

Nizet

2020

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Siglecs are sialic acid (Sia) recognizing immunoglobulin-like receptors expressed on the surface of all the major leukocyte lineages in mammals. Siglecs recognize ubiquitous Sia epitopes on various glycoconjugates in the cell glycocalyx and transduce signals to regulate immunological and inflammatory activities of these cells. The subset known as CD33-related Siglecs is principally inhibitory receptors that suppress leukocyte activation, and recent research has shown that a number of bacterial pathogens use Sia mimicry to engage these Siglecs as an immune evasion strategy. Conversely, Siglec-1 is a macrophage phagocytic receptor that engages GBS and other sialylated bacteria to promote effective phagocytosis and antigen presentation for the adaptive immune response, whereas certain viruses and parasites use Siglec-1 to gain entry to immune cells as a proximal step in the infectious process. Siglecs are positioned in crosstalk with other host innate immune sensing pathways to modulate the immune response to infection in complex ways. This chapter summarizes the current understanding of Siglecs at the host-pathogen interface, a field of study expanding in breadth and medical importance, and which provides potential targets for immune-based anti-infective strategies.

show abstract

Siglec‐1 inhibits RSV‐induced interferon gamma production by adult T cells in contrast to newborn T cells

Cited by 23 publications

References 35 publications

CD64 and CD169 could help differentiate bacterial from viral infections in Emergency Department

CD64 and CD169 could help differentiate bacterial from viral infections in Emergency Department

Norovirus Replication in Human Intestinal Epithelial Cells Is Restricted by the Interferon-Induced JAK/STAT Signaling Pathway and RNA Polymerase II-Mediated Transcriptional Responses

Siglecs at the Host–Pathogen Interface

Contact Info

Product

Resources

About