Human influenza virus infection elicits distinct patterns of monocyte and dendritic cell mobilization in blood and the nasopharynx

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 (HCs) 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 TNF alpha, IL-6, and IFN alpha in plasma and the nasopharynx than HCs. In blood, monocytes were the most frequent cellular source of TNF alpha 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.

Automated summary

The roles and functions of monocytes and dendritic cells (DCs) in the nasopharynx during respiratory viral infections, especially influenza A virus (IAV), are not completely understood. This study examined the frequencies and characteristics of circulating and nasopharyngeal monocytes and DCs in patients with IAV and other respiratory virus infections. The results showed that IAV patients had altered frequencies of monocytes and DCs compared to healthy controls, with increased accumulation of monocytes and DCs in the nasopharynx. Furthermore, older patients exhibited increased monocyte frequencies, suggesting a potential role in disease severity. Proteomic analysis also revealed differential expression of innate immunity-related proteins in IAV and SARS-CoV-2 patients. Overall, these findings provide insights into the tissue-specific and pathogen-specific patterns of monocyte and DC function during respiratory viral infections, emphasizing the importance of comparative investigations in different anatomical sites.