{"doi":"10.1101/2021.07.07.449660","title":"Defining the Immune Responses for SARS-CoV-2-Human Macrophage Interactions","abstract":"Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end organ malfunctions. All follow an abortive viral infection. To elucidate SARS-CoV-2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding consequent end-organ tissue damage.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":215494,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":629181,"name":"Pravin Yeapuri","orcid":null,"position":1,"is_corresponding":false},{"id":109778,"name":"Jatin Machhi","orcid":"0000-0001-6457-2022","position":2,"is_corresponding":false},{"id":810235,"name":"Katherine E. Olson","orcid":"0000-0001-6622-9922","position":3,"is_corresponding":false},{"id":659059,"name":"Farah Shahjin","orcid":"0000-0002-5645-4533","position":4,"is_corresponding":false},{"id":666658,"name":"You Zhou","orcid":"0000-0002-9783-1868","position":5,"is_corresponding":false},{"id":629182,"name":"Liang Jingjing","orcid":null,"position":6,"is_corresponding":false},{"id":297034,"name":"Kabita Pandey","orcid":null,"position":7,"is_corresponding":false},{"id":296005,"name":"Arpan Acharya","orcid":"0000-0003-2721-1062","position":8,"is_corresponding":false},{"id":69434,"name":"Siddappa N. Byrareddy","orcid":"0000-0002-6889-4640","position":9,"is_corresponding":false},{"id":266818,"name":"R. Lee Mosley","orcid":"0000-0002-4241-6149","position":10,"is_corresponding":false},{"id":109790,"name":"Howard E. Gendelman","orcid":"0000-0002-7831-0370","position":11,"is_corresponding":false},{"id":627856,"name":"Mai Mohamed Abdelmoaty","orcid":"0000-0001-7672-7052","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-18T23:52:55.971300Z","pmid":"34268510","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}