Early IFNß secretion determines variable downstream IL-12p70 responses upon TLR4 activation.
Cell Rep
; 39(13): 110989, 2022 06 28.
Статья
в английский
| MEDLINE | ID: covidwho-2121651
ABSTRACT
The interleukin-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bimodal IL-12p70 response to lipopolysaccharide (LPS) stimulation in healthy donors. Herein, we demonstrate that interferon ß (IFNß) is a major upstream determinant of IL-12p70 production, which is also associated with numbers and activation of circulating monocytes. Integrative modeling of proteomic, genetic, epigenomic, and cellular data confirms IFNß as key for LPS-induced IL-12p70 and allowed us to compare the relative effects of each of these parameters on variable cytokine responses. Clinical relevance of our findings is supported by reduced IFNß-IL-12p70 responses in patients hospitalized with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or chronically infected with hepatitis C (HCV). Importantly, these responses are resolved after viral clearance. Our systems immunology approach defines a better understanding of IL-12p70 and IFNß in healthy and infected persons, providing insights into how common genetic and epigenetic variation may impact immune responses to bacterial infection.
ключевые слова
Полный текст:
Имеется в наличии
Коллекция:
Международные базы данных
база данных:
MEDLINE
Основная тема:
Interferon-beta
/
Interleukin-12
/
Toll-Like Receptor 4
Тип исследования:
Прогностическое исследование
Пределы темы:
Люди
Язык:
английский
Журнал:
Cell Rep
Год:
2022
Тип:
Статья
Аффилированная страна:
J.celrep.2022.110989
Документы, близкие по теме
MEDLINE
...
LILACS
LIS