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Adv."],"published-print":{"date-parts":[[2026,1,30]]},"abstract":"<jats:p>\n                    If the immune system is an interconnected network, then the evolution of an archetype that is ideal for fighting one pathogen should result in trade-offs decreasing its ability to fight others. How many archetypes are there in an immune system? We infected diverse mice with\n                    <jats:italic toggle=\"yes\">Plasmodium chabaudi<\/jats:italic>\n                    and identified five distinct archetypes of responses on the basis of the host\u2019s position in microbial load, immune activity, and host damage space. To better understand the nature of these archetypes, we developed a mathematical model of a generalized host-pathogen system. This model explains the number and distribution of archetypes across a population of diverse hosts. Mice resilient to\n                    <jats:italic toggle=\"yes\">P. chabaudi<\/jats:italic>\n                    exhibited poor outcomes when challenged with influenza, SARS-CoV-1, or\n                    <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                    , and vice versa, supporting our trade-off hypothesis.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeb3911","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T18:59:52Z","timestamp":1769626792000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["From Plato to Pareto: Defining the shape of infection\u2019s disease space"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1865-7543","authenticated-orcid":true,"given":"Yael","family":"Lebel","sequence":"first","affiliation":[{"name":"Department of Molecular Cell Biology, Weizmann Institute, Rehovot, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6769-8702","authenticated-orcid":true,"given":"Avni S.","family":"Gupta","sequence":"additional","affiliation":[{"name":"University of Cincinnati Medical Center, Cincinnati, OH 45267, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5936-0302","authenticated-orcid":true,"given":"Victoria","family":"Chev\u00e9e","sequence":"additional","affiliation":[{"name":"University of Cincinnati Medical Center, Cincinnati, OH 45267, USA."},{"name":"Institut Pasteur, Universit\u00e9 de Paris Cit\u00e9, Inserm U1224, Microenvironment and Immunity Unit, 75015 Paris, France."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1121-5907","authenticated-orcid":true,"given":"Uri","family":"Alon","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology, Weizmann Institute, Rehovot, Israel."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2391-9963","authenticated-orcid":true,"given":"David S.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"G. 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