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

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.

Cellular and Transcriptional Signature of the Nasal Mucosa is Associated with Susceptibility to Pneumococcal Carriage in Older Adults

“…The nasal cell gene expression profiles suggested that older adults susceptible to pneumococcal colonization had higher levels of innate immune cell activation compared to protected older adults. Granulocytes are abundant in the nasal mucosa while monocytes are sparse with the later rapidly recruited after challenge in younger adults 9,24 .…”

“…Granulocytes are abundant in the nasal mucosa while monocytes are sparse with the later rapidly recruited after challenge in younger adults 9,24 .…”

“…Intermediate monocytes display an activated phenotype and are generally associated with more inflammatory conditions. Notably, they were enriched in the nasal mucosa of older adults but not younger adults infected with Influenza A virus and correlated with age 24 .…”

Acute Respiratory Illness Is Associated with Memory T Cell Differentiation and Other Immune Cell Changes in an Age-Associated Manner

“…Not surprisingly, monocytes were higher in infected individuals, probably due to the innate immune response and activation of these cells by proinflammatory cytokines associated with acute infection ( 21 ). Because we performed relative frequency analyses (using total live cells as the denominator), increases in monocytes and decreases in certain lymphocyte subsets such as B cells and CD94 + NK cells could contribute to the observed decrease in total lymphocytes in young infected individuals.…”

The role of dendritic cells in respiratory viral infection

“…The key cells required to initiate such a specific response to IAV are DCs. Studies in mice and in humans infected with IAV s howed that several subsets of DCs are recruited to and activated in the lung [ 28 , 47 , 48 ]. However, there were differences between the DC subsets.…”