{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T21:46:19Z","timestamp":1781732779523,"version":"3.54.5"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The complement system is designed to recognise and eliminate invading pathogens<jats:italic>via<\/jats:italic>activation of classical, alternative and lectin pathways. Human properdin stabilises the alternative pathway C3 convertase, resulting in an amplification loop that leads to the formation of C5 convertase, thereby acting as a positive regulator of the alternative pathway. It has been noted that human properdin on its own can operate as a pattern recognition receptor and exert immune functions outside its involvement in complement activation. Properdin can bind directly to microbial targets<jats:italic>via<\/jats:italic>DNA, sulfatides and glycosaminoglycans, apoptotic cells, nanoparticles, and well-known viral virulence factors. This study was aimed at investigating the complement-independent role of properdin against Influenza A virus infection. As one of the first immune cells to arrive at the site of IAV infection, we show here that IAV challenged neutrophils released properdin in a time-dependent manner. Properdin was found to directly interact with haemagglutinin, neuraminidase and matrix 1 protein Influenza A virus proteins in ELISA and western blot. Furthermore, modelling studies revealed that properdin could bind HA and NA of the H1N1 subtype with higher affinity compared to that of H3N2 due to the presence of an HA cleavage site in H1N1. In an infection assay using A549 cells, properdin suppressed viral replication in pH1N1 subtype while promoting replication of H3N2 subtype, as revealed by qPCR analysis of M1 transcripts. Properdin treatment triggered an anti-inflammatory response in H1N1-challenged A549 cells and a pro-inflammatory response in H3N2-infected cells, as evident from differential mRNA expression of TNF-\u03b1, NF-\u03baB, IFN-\u03b1, IFN-\u03b2, IL-6, IL-12 and RANTES. Properdin treatment also reduced luciferase reporter activity in MDCK cells transduced with H1N1 pseudotyped lentiviral particles; however, it was increased in the case of pseudotyped H3N2 particles. Collectively, we conclude that infiltrating neutrophils at the site of IAV infection can release properdin, which then acts as an entry inhibitor for pandemic H1N1 subtype while suppressing viral replication and inducing an anti-inflammatory response. H3N2 subtype can escape this immune restriction due to altered haemagglutinin and neuraminindase, leading to enhanced viral entry, replication and pro-inflammatory response. Thus, depending on the subtype, properdin can either limit or aggravate IAV infection in the host.<\/jats:p>","DOI":"10.3389\/fimmu.2021.747654","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T04:49:00Z","timestamp":1639025340000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Human Properdin Released By Infiltrating Neutrophils Can Modulate Influenza A Virus Infection"],"prefix":"10.3389","volume":"12","author":[{"given":"Praveen M.","family":"Varghese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuvechha","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futwan A.","family":"Al-Mohanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Souad M.","family":"Saleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad N.","family":"Almajhdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazar","family":"Beirag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saad H.","family":"Alkahtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Rajkumari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Nal Rogier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Sim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Idicula-Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taruna","family":"Madan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valarmathy","family":"Murugaiah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uday","family":"Kishore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2010.12.045","article-title":"Complement and Viral Pathogenesis","volume":"411","author":"Stoermer","year":"2011","journal-title":"Virology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01117","article-title":"Complement Evasion Strategies of Viruses: An Overview","volume":"8","author":"Agrawal","year":"2017","journal-title":"Front Microbiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2013.08.001","article-title":"Overview of Complement Activation and Regulation","volume":"33","author":"Noris","year":"2013","journal-title":"Semin Nephrol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/cr.2009.139","article-title":"Complement and Its Role in Innate and Adaptive Immune Responses","volume":"20","author":"Dunkelberger","year":"2010","journal-title":"Cell Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2003.11.029","article-title":"The Relevance of Complement to Virus Biology","volume":"319","author":"Blue","year":"2004","journal-title":"Virology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/s0167-5699(98)01376-0","article-title":"Does Properdin Crosslink the Cellular and the Humoral Immune Response","volume":"20","author":"Schwaeble","year":"1999","journal-title":"Immunol Today"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-05-089821","article-title":"Activator-Specific Requirement of Properdin in the Initiation and Amplification of the Alternative Pathway Complement","volume":"111","author":"Kimura","year":"2008","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200104053441406","article-title":"Complement. 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