Abstract
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.
Highlights
The C-X-C motif chemokine ligand 17 (CXCL17) is a mucosal chemokine expressed in the respiratory tract under both homeostatic and inflammatory conditions [1,2,3]
Dyspnea, rhinorrhea, and sputum production were more common during influenza, whereas dry cough and vomit were more frequent among COVID-19 patients (Table 1)
Our results indicate that CXCL17 levels were significatively elevated in the serum of influenza cases, but not in healthy donors (HD) or COVID-19 subjects
Summary
The C-X-C motif chemokine ligand 17 (CXCL17) is a mucosal chemokine expressed in the respiratory tract under both homeostatic and inflammatory conditions [1,2,3]. Its functions are less well characterized, it has been reported to promote anti-inflammatory activities and likely prevent autoimmunity [2, 4]. CXCL17 exhibits broad antimicrobial activity [2, 4], suggesting that it may play an important role in protective immunity against respiratory pathogens. There is only a report suggesting that CXCL17 participates in immunity against genitourinary herpes infections [5]. Despite CXCL17 being one of the most highly expressed chemokines in the human lung, its potential role in human respiratory infections has not been studied
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