Human influenza virus infection elicits distinct patterns of monocyte and dendritic cell mobilization in blood and the nasopharynx
- Karolinska Institute, Sweden
- SomaLogic, United States
- Boulder Bioconsulting Inc, United States
Abstract
During respiratory viral infections, the precise roles of monocytes and dendritic cells (DCs) in the nasopharynx in limiting infection and influencing disease severity are incompletely described. We studied circulating and nasopharyngeal monocytes and DCs in healthy controls (HC) and in patients with mild to moderate infections (primarily influenza A virus, IAV). As compared to HCs, patients with acute IAV infection displayed reduced DC but increased intermediate monocytes frequencies in blood, and an accumulation of most monocyte and DC subsets in the nasopharynx. IAV patients had more mature monocytes and DCs in the nasopharynx, and higher levels of TNFα, IL-6 and IFNα in plasma and the nasopharynx than HCs. In blood, monocytes were the most frequent cellular source of TNFα during IAV infection and remained responsive to additional stimulation with TLR7/8L. Immune responses in older patients skewed towards increased monocyte frequencies rather than DCs, suggesting a contributory role for monocytes in disease severity. In patients with other respiratory virus infections, we observed changes in monocyte and DC frequencies in the nasopharynx distinct from IAV patients, while differences in blood were more similar across infection groups. Using SomaScan, a high-throughput aptamer-based assay to study proteomic changes between patients and HCs, we found differential expression of innate immunity-related proteins in plasma and nasopharyngeal secretions of IAV and SARS-CoV-2 patients. Together, our findings demonstrate tissue-specific and pathogen-specific patterns of monocyte and DC function during human respiratory viral infections and highlight the importance of comparative investigations in blood and the nasopharynx.
Data availability
Source Data files have been provided for figures 1-7 and Appendix 2_Table 2 as separate excel files.
Article and author information
Author details
Anna Smed-Sörensen
Funding
Vetenskapsrådet
- Anna Smed-Sörensen
Hjärt-Lungfonden
- Anna Smed-Sörensen
Bill and Melinda Gates Foundation
- Anna Smed-Sörensen
Barncancerfonden
- Anna Smed-Sörensen
Karolinska Institutet
- Anna Smed-Sörensen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Informed consent was obtained from all patients and volunteers following verbal and written information. The study was approved by the Swedish Ethical Review Authority (No. 2015/1949-31/4) and performed according to the Declaration of Helsinki.
Copyright
© 2023, Vangeti et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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