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He rightly stressed that only a small minority of individuals infected by almost any microbe develop clinical disease. Intriguingly, though, he did not mention the abundant and elegant findings reported from 1905 onward that unambiguously pointed to host genetic determinants of infection outcome in plants and animals, including human inborn errors of immunity. Diverse findings over the next 50\u00a0y corroborated and extended these earlier genetic and immunological observations that Ren\u00e9 Dubos had neglected. Meanwhile, the sequential advent of immunosuppression- and HIV\u2013driven immunodeficiencies unexpectedly provided a mechanistic basis for his own views. Collectively, these two lines of evidence support a host theory of infectious diseases, with inherited and acquired immunodeficiencies as the key determinants of severe infection outcome, relegating the germ to an environmental trigger that reveals an underlying and preexisting cause of disease and death.<\/jats:p>","DOI":"10.1073\/pnas.2301186120","type":"journal-article","created":{"date-parts":[[2023,6,12]],"date-time":"2023-06-12T15:21:04Z","timestamp":1686583264000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":20,"title":["From second thoughts on the germ theory to a full-blown host theory"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7782-4169","authenticated-orcid":false,"given":"Jean-Laurent","family":"Casanova","sequence":"first","affiliation":[{"name":"HHMI, New York, NY 10065"},{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,6,12]]},"reference":[{"key":"e_1_3_5_1_2","doi-asserted-by":"crossref","unstructured":"C. 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