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The attributed reason is the inheritance of a set of immune system genes that can efficiently deal with the pathogens. In this study, we show how outbred mice differentially respond to\n              <jats:italic>Cryptococcus neoformans,<\/jats:italic>\n              a fungal pathogen, and the mechanism through which the surviving mice mount a protective immune defense. We identified that those mice developing antibodies specifically against Pep1p, an aspartic protease secreted by\n              <jats:italic>C. neoformans<\/jats:italic>\n              , had significantly improved survival. Vaccination (either prophylactic or therapeutic) with a recombinant Pep1p significantly increased the survival of the mice by decreasing the fungal load and stimulating a protective immune response. Passive immunization of\n              <jats:italic>C. neoformans-<\/jats:italic>\n              infected mice with monoclonal antibodies developed against Pep1p also improves the survival of the mice by increasing phagocytosis of\n              <jats:italic>C. neoformans<\/jats:italic>\n              and decreasing the multiplication of this fungus. Together, these data demonstrate the prophylactic and therapeutic potentials of the\n              <jats:italic>C. neoformans<\/jats:italic>\n              antigenic protein Pep1p or Pep1p-specific antibodies against this fungal infection. Also, this study suggests that the immunological interaction and thereby the responses developed against a pathogen guide the hosts to behave differentially against microbial pathogenicity.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Vaccination and immunotherapies against fungal pathogens still remain a challenge. Here, we show using an\n              <jats:italic>in vivo<\/jats:italic>\n              model based on outbred mice that development of antibodies against Pep1p, an antigenic protein of the fungal pathogen\n              <jats:italic>Cryptococcus neoformans<\/jats:italic>\n              , confers resistance to this fungal infection. In support of this observation, prophylactic or therapeutic immunization of the mice with recombinant Pep1p could improve their survival when infected with a lethal dose of\n              <jats:italic>C. neoformans<\/jats:italic>\n              . Moreover, passive therapy with monoclonal anti-Pep1p antibodies also enhanced survival of the mice from\n              <jats:italic>C. neoformans<\/jats:italic>\n              infection. The associated antifungal mechanisms were mounting of a protective immune response and the development of fungal specific antibodies that decrease the fungal burden due to an increase in their phagocytosis and\/or inhibit the fungal multiplication. Together, our study demonstrates (a) the mode of host\u2013fungal interaction and the immune response developed thereby play a crucial role in developing resistance against\n              <jats:italic>C. neoformans<\/jats:italic>\n              ; (b) Pep1p, an aspartic protease as well as an antigenic protein secreted by\n              <jats:italic>C. neoformans<\/jats:italic>\n              , can be exploited for vaccination (both prophylactic and therapeutic) or immunotherapy to improve the host defense during this fungal infection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.02733-24","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T13:00:55Z","timestamp":1729688455000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["<i>Cryptococcus neoformans<\/i>\n            infections: aspartyl protease potential to improve outcome in susceptible hosts"],"prefix":"10.1128","volume":"15","author":[{"given":"Fr\u00e9d\u00e9rique","family":"Vernel-Pauillac","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS, Molecular Mycology Unit, UMR 2000, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Laurent-Winter","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS UAR 2024, Mass Spectrometry for Biology Unit, Proteomics platform, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Fiette","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Human Histopathology and Animal Models Unit, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilhem","family":"Janbon","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS, Molecular Mycology Unit, UMR 2000, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5813-7497","authenticated-orcid":true,"given":"Vishukumar","family":"Aimanianda","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS, Molecular Mycology Unit, UMR 2000, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1671-1475","authenticated-orcid":true,"given":"Fran\u00e7oise","family":"Dromer","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, CNRS, Molecular Mycology Unit, UMR 2000, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2015.10.006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2311057"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00499-6"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00731-4"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-10-199"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2004.12.004"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz193"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38238-6"},{"key":"e_1_3_3_10_2","first-page":"61","article-title":"Cryptococcal infections in non-HIV-infected patients","volume":"124","author":"Pappas PG","year":"2013","unstructured":"Pappas PG. 2013. 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