Rare variants in Toll-like receptor 7 results in functional impairment and downregulation of cytokine-mediated signaling in COVID-19 patients.
Journal
Genes and immunity
ISSN: 1476-5470
Titre abrégé: Genes Immun
Pays: England
ID NLM: 100953417
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
10
09
2021
accepted:
22
11
2021
revised:
11
11
2021
pubmed:
26
12
2021
medline:
1
3
2022
entrez:
25
12
2021
Statut:
ppublish
Résumé
Toll-like receptors (TLR) are crucial components in the initiation of innate immune responses to a variety of pathogens, triggering the production of pro-inflammatory cytokines and type I and II interferons, which are responsible for innate antiviral responses. Among the different TLRs, TLR7 recognizes several single-stranded RNA viruses including SARS-CoV-2. We and others identified rare loss-of-function variants in X-chromosomal TLR7 in young men with severe COVID-19 and with no prior history of major chronic diseases, that were associated with impaired TLR7 signaling as well as type I and II IFN responses. Here, we performed RNA sequencing to investigate transcriptome variations following imiquimod stimulation of peripheral blood mononuclear cells isolated from patients carrying previously identified hypomorphic, hypofunctional, and loss-of-function TLR7 variants. Our investigation revealed a profound impairment of the TLR7 pathway in patients carrying loss-of-function variants. Of note, a failure in IFNγ upregulation following stimulation was also observed in cells harboring the hypofunctional and hypomorphic variants. We also identified new TLR7 variants in severely affected male patients for which a functional characterization of the TLR7 pathway was performed demonstrating a decrease in mRNA levels in the IFNα, IFNγ, RSAD2, ACOD1, IFIT2, and CXCL10 genes.
Identifiants
pubmed: 34952932
doi: 10.1038/s41435-021-00157-1
pii: 10.1038/s41435-021-00157-1
pmc: PMC8703210
doi:
Substances chimiques
Cytokines
0
TLR7 protein, human
0
Toll-Like Receptor 7
0
Toll-Like Receptor 8
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
51-56Investigateurs
Francesca Montagnani
(F)
Mario Tumbarello
(M)
Ilaria Rancan
(I)
Massimiliano Fabbiani
(M)
Barbara Rossetti
(B)
Laura Bergantini
(L)
Miriana D'Alessandro
(M)
Paolo Cameli
(P)
David Bennett
(D)
Federico Anedda
(F)
Simona Marcantonio
(S)
Sabino Scolletta
(S)
Federico Franchi
(F)
Maria Antonietta Mazzei
(MA)
Susanna Guerrini
(S)
Edoardo Conticini
(E)
Luca Cantarini
(L)
Bruno Frediani
(B)
Danilo Tacconi
(D)
Chiara Spertilli Raffaelli
(CS)
Marco Feri
(M)
Alice Donati
(A)
Raffaele Scala
(R)
Luca Guidelli
(L)
Genni Spargi
(G)
Marta Corridi
(M)
Cesira Nencioni
(C)
Leonardo Croci
(L)
Gian Piero Caldarelli
(GP)
Davide Romani
(D)
Paolo Piacentini
(P)
Maria Bandini
(M)
Elena Desanctis
(E)
Silvia Cappelli
(S)
Anna Canaccini
(A)
Agnese Verzuri
(A)
Valentina Anemoli
(V)
Manola Pisani
(M)
Agostino Ognibene
(A)
Alessandro Pancrazzi
(A)
Maria Lorubbio
(M)
Massimo Vaghi
(M)
Antonella D'Arminio Monforte
(A)
Federica Gaia Miraglia
(FG)
Raffaele Bruno
(R)
Marco Vecchia
(M)
Massimo Girardis
(M)
Sophie Venturelli
(S)
Stefano Busani
(S)
Andrea Cossarizza
(A)
Andrea Antinori
(A)
Alessandra Vergori
(A)
Arianna Emiliozzi
(A)
Stefano Rusconi
(S)
Matteo Siano
(M)
Arianna Gabrieli
(A)
Agostino Riva
(A)
Daniela Francisci
(D)
Elisabetta Schiaroli
(E)
Francesco Paciosi
(F)
Andrea Tommasi
(A)
Pier Giorgio Scotton
(PG)
Francesca Andretta
(F)
Sandro Panese
(S)
Stefano Baratti
(S)
Renzo Scaggiante
(R)
Francesca Gatti
(F)
Saverio Giuseppe Parisi
(SG)
Francesco Castelli
(F)
Eugenia Quiros-Roldan
(E)
Melania Degli Antoni
(MD)
Isabella Zanella
(I)
Matteo Della Monica
(M)
Carmelo Piscopo
(C)
Mario Capasso
(M)
Roberta Russo
(R)
Immacolata Andolfo
(I)
Achille Iolascon
(A)
Giuseppe Fiorentino
(G)
Massimo Carella
(M)
Marco Castori
(M)
Filippo Aucella
(F)
Pamela Raggi
(P)
Rita Perna
(R)
Matteo Bassetti
(M)
Antonio Di Biagio
(A)
Maurizio Sanguinetti
(M)
Luca Masucci
(L)
Alessandra Guarnaccia
(A)
Serafina Valente
(S)
Oreste De Vivo
(O)
Gabriella Doddato
(G)
Mirjam Lista
(M)
Giada Beligni
(G)
Floriana Valentino
(F)
Kristina Zguro
(K)
Rossella Tita
(R)
Annarita Giliberti
(A)
Maria Antonietta Mencarelli
(MA)
Caterina Lo Rizzo
(CL)
Anna Maria Pinto
(AM)
Francesca Ariani
(F)
Laura Di Sarno
(L)
Elena Bargagli
(E)
Marco Mandalà
(M)
Alessia Giorli
(A)
Lorenzo Salerni
(L)
Patrizia Zucchi
(P)
Pierpaolo Parravicini
(P)
Elisabetta Menatti
(E)
Tullio Trotta
(T)
Ferdinando Giannattasio
(F)
Gabriella Coiro
(G)
Fabio Lena
(F)
Gianluca Lacerenza
(G)
Cristina Mussini
(C)
Enrico Martinelli
(E)
Luisa Tavecchia
(L)
Mary Ann Belli
(MA)
Lia Crotti
(L)
Gianfranco Parati
(G)
Maurizio Sanarico
(M)
Francesco Raimondi
(F)
Filippo Biscarini
(F)
Alessandra Stella
(A)
Tiziana Bachetti
(T)
Maria Teresa La Rovere
(MT)
Serena Ludovisi
(S)
Maurizio Bussotti
(M)
Simona Dei
(S)
Sabrina Ravaglia
(S)
Rosangela Artuso
(R)
Elena Andreucci
(E)
Giulia Gori
(G)
Angelica Pagliazzi
(A)
Erika Fiorentini
(E)
Antonio Perrella
(A)
Francesco Bianchi
(F)
Paola Bergomi
(P)
Emanuele Catena
(E)
Riccardo Colombo
(R)
Sauro Luchi
(S)
Giovanna Morelli
(G)
Paola Petrocelli
(P)
Sarah Iacopini
(S)
Sara Modica
(S)
Silvia Baroni
(S)
Francesco Vladimiro Segala
(FV)
Marco Falcone
(M)
Giusy Tiseo
(G)
Chiara Barbieri
(C)
Tommaso Matucci
(T)
Davide Grassi
(D)
Claudio Ferri
(C)
Franco Marinangeli
(F)
Francesco Brancati
(F)
Antonella Vincenti
(A)
Valentina Borgo
(V)
Stefania Lombardi
(S)
Mirco Lenzi
(M)
Massimo Antonio Di Pietro
(MA)
Francesca Vichi
(F)
Benedetta Romanin
(B)
Letizia Attala
(L)
Cecilia Costa
(C)
Andrea Gabbuti
(A)
Roberto Menè
(R)
Marta Colaneri
(M)
Patrizia Casprini
(P)
Giuseppe Merla
(G)
Gabriella Maria Squeo
(GM)
Marcello Maffezzoni
(M)
Informations de copyright
© 2021. The Author(s).
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