TY - JOUR
T1 - CXCL17 Is a Specific Diagnostic Biomarker for Severe Pandemic Influenza A(H1N1) That Predicts Poor Clinical Outcome
AU - Choreño-Parra, Jose Alberto
AU - Jiménez-Álvarez, Luis Armando
AU - Ramírez-Martínez, Gustavo
AU - Sandoval-Vega, Montserrat
AU - Salinas-Lara, Citlaltepetl
AU - Sánchez-Garibay, Carlos
AU - Luna-Rivero, Cesar
AU - Hernández-Montiel, Erika Mariana
AU - Fernández-López, Luis Alejandro
AU - Cabrera-Cornejo, María Fernanda
AU - Choreño-Parra, Eduardo Misael
AU - Cruz-Lagunas, Alfredo
AU - Domínguez, Andrea
AU - Márquez-García, Eduardo
AU - Cabello-Gutiérrez, Carlos
AU - Bolaños-Morales, Francina Valezka
AU - Mena-Hernández, Lourdes
AU - Delgado-Zaldivar, Diego
AU - Rebolledo-García, Daniel
AU - Guadarrama-Ortiz, Parménides
AU - Regino-Zamarripa, Nora E.
AU - Mendoza-Milla, Criselda
AU - García-Latorre, Ethel A.
AU - Rodiguez-Reyna, Tatiana Sofia
AU - Cervántes-Rosete, Diana
AU - Hernández-Cárdenas, Carmen M.
AU - Khader, Shabaana A.
AU - Zlotnik, Albert
AU - Zúñiga, Joaquín
N1 - Publisher Copyright:
© Copyright © 2021 Choreño-Parra, Jiménez-Álvarez, Ramírez-Martínez, Sandoval-Vega, Salinas-Lara, Sánchez-Garibay, Luna-Rivero, Hernández-Montiel, Fernández-López, Cabrera-Cornejo, Choreño-Parra, Cruz-Lagunas, Domínguez, Márquez-García, Cabello-Gutiérrez, Bolaños-Morales, Mena-Hernández, Delgado-Zaldivar, Rebolledo-García, Guadarrama-Ortiz, Regino-Zamarripa, Mendoza-Milla, García-Latorre, Rodiguez-Reyna, Cervántes-Rosete, Hernández-Cárdenas, Khader, Zlotnik and Zúñiga.
PY - 2021/2/26
Y1 - 2021/2/26
N2 - The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.
AB - The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.
KW - COVID-19
KW - CXCL17
KW - SARS-CoV-2
KW - chemokines
KW - influenza A(H1N1)
KW - tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85102576975&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.633297
DO - 10.3389/fimmu.2021.633297
M3 - Article
C2 - 33717172
AN - SCOPUS:85102576975
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 633297
ER -