TY - JOUR
T1 - Systems Immunology Approaches to Understanding Immune Responses in Acute Infection of Yellow Fever Patients
AU - Gonçalves, André N.A.
AU - Costa, Priscilla R.
AU - Thomazella, Mateus V.
AU - Correia, Carolina A.
AU - Marmorato, Mariana P.
AU - Dias, Juliana Z.C.
AU - Silveira, Cassia G.T.
AU - Maestri, Alvino
AU - Cerqueira, Natalia B.
AU - Moreira, Carlos H.V.
AU - Buccheri, Renata
AU - Félix, Alvina C.
AU - Martins, Felipe M.
AU - Maso, Vanessa E.
AU - Ferreira, Frederico M.
AU - Araújo, José D.A.
AU - Vasconcelos, Amanda P.
AU - Gonzalez-Dias, Patrícia
AU - Pelletier, Adam Nicolas
AU - Sékaly, Rafick Pierre
AU - Cabral-Marques, Otavio
AU - Coelho-dos-Reis, Jordana G.A.
AU - Ferreira, Daniela
AU - Kallas, Esper G.
AU - Nakaya, Helder I.
PY - 2024/12/1
Y1 - 2024/12/1
N2 - In the 2018 yellow fever (YF) outbreak in Brazil, we generated new transcriptomic data and combined it with clinical and immunological data to decode the pathogenesis of YF. Analyzing 79 patients, we found distinct gene expression patterns between acute YF, other viral infections, and the milder YF-17D vaccine infection. We identified a critical role for low-density, immature neutrophils in severe outcomes, marked by the downregulation of genes essential for neutrophil migration and maturation, such as PADI4, CSF3R, and ICAM1, in deceased patients. Our study also revealed complex interactions among inflammation-related genes, including increased CXCL10 and IL1R2 expression and decreased IL-1b expression in the acute phase. The diminished expression of HLA class II genes indicates impaired antigen presentation. These findings highlight the delicate balance of immune responses in YF pathogenesis and lay the groundwork for future therapeutic and diagnostic advancements.
AB - In the 2018 yellow fever (YF) outbreak in Brazil, we generated new transcriptomic data and combined it with clinical and immunological data to decode the pathogenesis of YF. Analyzing 79 patients, we found distinct gene expression patterns between acute YF, other viral infections, and the milder YF-17D vaccine infection. We identified a critical role for low-density, immature neutrophils in severe outcomes, marked by the downregulation of genes essential for neutrophil migration and maturation, such as PADI4, CSF3R, and ICAM1, in deceased patients. Our study also revealed complex interactions among inflammation-related genes, including increased CXCL10 and IL1R2 expression and decreased IL-1b expression in the acute phase. The diminished expression of HLA class II genes indicates impaired antigen presentation. These findings highlight the delicate balance of immune responses in YF pathogenesis and lay the groundwork for future therapeutic and diagnostic advancements.
KW - PBMC transcriptome
KW - system biology analysis
KW - yellow fever infection
U2 - 10.1002/jmv.70099
DO - 10.1002/jmv.70099
M3 - Article
SN - 0146-6615
VL - 96
JO - Journal of Medical Virology
JF - Journal of Medical Virology
IS - 12
M1 - e70099
ER -
