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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\u03b1, IL-6, and IFN\u03b1 in plasma and the nasopharynx than HCs. In blood, monocytes were the most frequent cellular source of TNF\u03b1 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.<\/jats:p>","DOI":"10.7554\/elife.77345","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T08:01:25Z","timestamp":1675843285000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.77345","source":"Crossref","is-referenced-by-count":26,"title":["Human influenza virus infection elicits distinct patterns of monocyte and dendritic cell mobilization in blood and the nasopharynx"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3404-6878","authenticated-orcid":true,"given":"Sindhu","family":"Vangeti","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00m8d6786","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Immunology and Allergy, Department of Medicine 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