Identification of cellular sources and molecular pathways driving the acute antiviral and inflammatory response in response to SARS-CoV-2 infection is critical to develop targeted treatment and mitigate COVID-19 severity. Here we show that in COVID-19 patients, circulating plasmacytoid dendritic cells (pDCs) decline early after symptom onset but reemerge after viral clearance. This transient depletion coincides with decreased expression of the systemic inflammatory cytokines CXCL10 and IL-6. Using an in vitro stem cell-based human pDC model, we demonstrate that pDCs sense SARS-CoV-2 and in response produce multiple antiviral (IFNα and IFNλ1) and inflammatory (IL-6, IL-8, CXCL10) cytokines. This immune response is sufficient to protect epithelial cells from de novoSARS-CoV-2 infection. Disruption of major innate sensing pathways identified TLR7-MyD88 signaling as the pathway predominantly responsible for antiviral IFNs whereas TLR2 is responsible for the inflammatory IL-6 response. Importantly, SARS-CoV-2 engages the neuropilin-1 receptor to mitigate expression of IFNα but not IL-6 by the pDCs.

Identification of cellular sources and molecular pathways driving the acute antiviral and inflammatory response in response to SARS-CoV-2 infection is critical to develop targeted treatment and mitigate COVID-19 severity. Here we show that in COVID-19 patients, circulating plasmacytoid dendritic cells (pDCs) decline early after symptom onset but reemerge after viral clearance. This transient depletion coincides with decreased expression of the systemic inflammatory cytokines CXCL10 and IL-6. Using an in vitro stem cell-based human pDC model, we demonstrate that pDCs sense SARS-CoV-2 and in response produce multiple antiviral (IFNα and IFNλ1) and inflammatory (IL-6, IL-8, CXCL10) cytokines. This immune response is sufficient to protect epithelial cells from _de novo_SARS-CoV-2 infection. Disruption of major innate sensing pathways identified TLR7-MyD88 signaling as the pathway predominantly responsible for antiviral IFNs whereas TLR2 is responsible for the inflammatory IL-6 response. Importantly, SARS-CoV-2 engages the neuropilin-1 receptor to mitigate expression of IFNα but not IL-6 by the pDCs.

Plasmacytoid dendritic cells sense SARS-CoV-2 through TLR2-IL6 and TLR7-INFα pathways that protect epithelial cells from infection

Exploring the intricacies of host-pathogen communication is vital in order to understand why
some microbes persist within a host, while others are effectively cleared. As such,
host-pathogen communication is an urgent area of research underpinning human health
and disease, especially given the emerging concerns of antibiotic resistance.
Understanding host-pathogen pathways requires intricate knowledge in the fields of both
microbiology and immunology.

Living in a world of specialists, where scientists sometimes invest their whole career
studying one organism, a specific pathway or a protein, multidisciplinary discussions of
host-pathogen interactions are highly needed. This international conference will provide
such a forum for scientific exchange at the highest level, between scientists from different
research areas related to host-pathogen interactions, with the aim to trigger fruitful
collaborations addressing the urgent questions in the field.

This meeting has an additional special focus of bringing researchers from Ireland, Denmark
and Israel together to learn about cutting edge biology and form new collaborations.
Thus, the conference will be a showcase for the exciting and original research emanating
from these three small but innovative countries.

Host-Pathogen Communication (HPC) 2021

Awards & close

Initiation and Regulation of Innate Immunity

Mouse models carrying patient-derived mutations in IRF3 and TBK1 enable mechanistic characterization of herpes simplex encephalitis

A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection

Coordinating immune-defence functions of MLKL: endosomal targeting of MLKL by site specific ubiquitination facilitates lysosomal destruction of intracellular pathogenes