tetano
Editor, Senior Moderator
Nat Immunol
. 2022 Jan 31.
doi: 10.1038/s41590-021-01114-w. Online ahead of print.
Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules
Matteo Stravalaci[SUP] #[/SUP][SUP] 1 2 [/SUP], Isabel Pagani[SUP] #[/SUP][SUP] 3 [/SUP], Elvezia Maria Paraboschi[SUP] 1 2 [/SUP], Mattia Pedotti[SUP] 4 [/SUP], Andrea Doni[SUP] 1 [/SUP], Francesco Scavello[SUP] 1 [/SUP], Sarah N Mapelli[SUP] 1 [/SUP], Marina Sironi[SUP] 1 [/SUP], Chiara Perucchini[SUP] 1 [/SUP], Luca Varani[SUP] 4 [/SUP], Milos Matkovic[SUP] 4 [/SUP], Andrea Cavalli[SUP] 4 5 [/SUP], Daniela Cesana[SUP] 6 [/SUP], Pierangela Gallina[SUP] 6 [/SUP], Nicoletta Pedemonte[SUP] 7 [/SUP], Valeria Capurro[SUP] 7 [/SUP], Nicola Clementi[SUP] 8 [/SUP], Nicasio Mancini[SUP] 8 [/SUP], Pietro Invernizzi[SUP] 9 10 [/SUP], Rafael Bayarri-Olmos[SUP] 11 [/SUP], Peter Garred[SUP] 11 [/SUP], Rino Rappuoli[SUP] 12 13 [/SUP], Stefano Duga[SUP] 1 2 [/SUP], Barbara Bottazzi[SUP] 1 [/SUP], Mariagrazia Uguccioni[SUP] 2 4 [/SUP], Rosanna Asselta[SUP] 1 2 [/SUP], Elisa Vicenzi[SUP] 14 [/SUP], Alberto Mantovani[SUP] 15 16 17 [/SUP], Cecilia Garlanda[SUP] 18 19 [/SUP]
Affiliations
Abstract
The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral nucleocapsid and spike proteins, respectively. MBL bound trimeric spike protein, including that of variants of concern (VoC), in a glycan-dependent manner and inhibited SARS-CoV-2 in three in vitro models. Moreover, after binding to spike protein, MBL activated the lectin pathway of complement activation. Based on retention of glycosylation sites and modeling, MBL was predicted to recognize the Omicron VoC. Genetic polymorphisms at the MBL2 locus were associated with disease severity. These results suggest that selected humoral fluid-phase PRMs can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.
. 2022 Jan 31.
doi: 10.1038/s41590-021-01114-w. Online ahead of print.
Recognition and inhibition of SARS-CoV-2 by humoral innate immunity pattern recognition molecules
Matteo Stravalaci[SUP] #[/SUP][SUP] 1 2 [/SUP], Isabel Pagani[SUP] #[/SUP][SUP] 3 [/SUP], Elvezia Maria Paraboschi[SUP] 1 2 [/SUP], Mattia Pedotti[SUP] 4 [/SUP], Andrea Doni[SUP] 1 [/SUP], Francesco Scavello[SUP] 1 [/SUP], Sarah N Mapelli[SUP] 1 [/SUP], Marina Sironi[SUP] 1 [/SUP], Chiara Perucchini[SUP] 1 [/SUP], Luca Varani[SUP] 4 [/SUP], Milos Matkovic[SUP] 4 [/SUP], Andrea Cavalli[SUP] 4 5 [/SUP], Daniela Cesana[SUP] 6 [/SUP], Pierangela Gallina[SUP] 6 [/SUP], Nicoletta Pedemonte[SUP] 7 [/SUP], Valeria Capurro[SUP] 7 [/SUP], Nicola Clementi[SUP] 8 [/SUP], Nicasio Mancini[SUP] 8 [/SUP], Pietro Invernizzi[SUP] 9 10 [/SUP], Rafael Bayarri-Olmos[SUP] 11 [/SUP], Peter Garred[SUP] 11 [/SUP], Rino Rappuoli[SUP] 12 13 [/SUP], Stefano Duga[SUP] 1 2 [/SUP], Barbara Bottazzi[SUP] 1 [/SUP], Mariagrazia Uguccioni[SUP] 2 4 [/SUP], Rosanna Asselta[SUP] 1 2 [/SUP], Elisa Vicenzi[SUP] 14 [/SUP], Alberto Mantovani[SUP] 15 16 17 [/SUP], Cecilia Garlanda[SUP] 18 19 [/SUP]
Affiliations
- PMID: 35102342
- DOI: 10.1038/s41590-021-01114-w
Abstract
The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral nucleocapsid and spike proteins, respectively. MBL bound trimeric spike protein, including that of variants of concern (VoC), in a glycan-dependent manner and inhibited SARS-CoV-2 in three in vitro models. Moreover, after binding to spike protein, MBL activated the lectin pathway of complement activation. Based on retention of glycosylation sites and modeling, MBL was predicted to recognize the Omicron VoC. Genetic polymorphisms at the MBL2 locus were associated with disease severity. These results suggest that selected humoral fluid-phase PRMs can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.