{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:27:53Z","timestamp":1790123273643,"version":"4.0.1"},"reference-count":235,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31870001"],"award-info":[{"award-number":["31870001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["JCYJ20210324122802006"],"award-info":[{"award-number":["JCYJ20210324122802006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["JCYJ20220530144811025"],"award-info":[{"award-number":["JCYJ20220530144811025"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Science and Technology Innovation Commission Fund","award":["31870001"],"award-info":[{"award-number":["31870001"]}]},{"name":"Shenzhen Science and Technology Innovation Commission Fund","award":["JCYJ20210324122802006"],"award-info":[{"award-number":["JCYJ20210324122802006"]}]},{"name":"Shenzhen Science and Technology Innovation Commission Fund","award":["JCYJ20220530144811025"],"award-info":[{"award-number":["JCYJ20220530144811025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Pathogenic species of Legionella can infect human alveolar macrophages through Legionella-containing aerosols to cause a disease called Legionellosis, which has two forms: a flu-like Pontiac fever and severe pneumonia named Legionnaires\u2019 disease (LD). Legionella is an opportunistic pathogen that frequently presents in aquatic environments as a biofilm or protozoa parasite. Long-term interaction and extensive co-evolution with various genera of amoebae render Legionellae pathogenic to infect humans and also generate virulence differentiation and heterogeneity. Conventionally, the proteins involved in initiating replication processes and human macrophage infections have been regarded as virulence factors and linked to pathogenicity. However, because some of the virulence factors are associated with the infection of protozoa and macrophages, it would be more accurate to classify them as survival factors rather than virulence factors. Given that the molecular basis of virulence variations among non-pathogenic, pathogenic, and highly pathogenic Legionella has not yet been elaborated from the perspective of virulence factors, a comprehensive explanation of how Legionella infects its natural hosts, protozoans, and accidental hosts, humans is essential to show a novel concept regarding the virulence factor of Legionella. In this review, we overviewed the pathogenic development of Legionella from protozoa, the function of conventional virulence factors in the infections of protozoa and macrophages, the host\u2019s innate immune system, and factors involved in regulating the host immune response, before discussing a probably new definition for the virulence factors of Legionella.<\/jats:p>","DOI":"10.3390\/microorganisms11010074","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T08:42:22Z","timestamp":1672216942000},"page":"74","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Concept about the Virulence Factor of Legionella"],"prefix":"10.3390","volume":"11","author":[{"given":"Jin-Lei","family":"Yang","sequence":"first","affiliation":[{"name":"The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Li","sequence":"additional","affiliation":[{"name":"The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5809-7904","authenticated-orcid":false,"given":"Xiao-Yong","family":"Zhan","sequence":"additional","affiliation":[{"name":"The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1128\/CMR.15.3.506-526.2002","article-title":"Legionella and Legionnaires\u2019 disease: 25 years of investigation","volume":"15","author":"Fields","year":"2002","journal-title":"Clin. 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