Enhanced TLR7-dependent production of type I interferon by pDCs underlies pandemic chilblains

The Journal of Experimental Medicine, Journal Year: 2025, Volume and Issue: 222(7)

Published: April 14, 2025

Outbreaks of chilblains were reported during the COVID-19 pandemic. Given essential role type I interferon (I-IFN) in protective immunity against SARS-CoV-2 and association with inherited interferonopathies, we hypothesized that excessive I-IFN responses to might underlie occurrence this context. We identified a transient signature chilblain lesions, accompanied by an acral infiltration activated plasmacytoid dendritic cells (pDCs). Patients otherwise asymptomatic or had mild disease without seroconversion. Their leukocytes produced abnormally high levels upon TLR7 stimulation agonists ssRNA viruses—particularly SARS-CoV-2—but not DNA TLR9 dsDNA virus HSV-1. Moreover, patients’ pDCs displayed cell-intrinsic hyperresponsiveness regardless levels. Inherited deficiency confers predisposition life-threatening COVID-19. Conversely, our findings suggest enhanced activity predisposed individuals could confer innate, pDC-mediated, sterilizing infection, I-IFN–driven as trade-off.

Language: Английский

Discordant Outcomes of SARS-CoV-2 Infection in Household Contacts

Published: Jan. 1, 2025

Language: Английский