{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:33:29Z","timestamp":1787772809396,"version":"build-2784847793"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":768,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Circulating IgM present in the body prior to any apparent Ag exposure is referred to as natural IgM. Natural IgM provides protective immunity against a variety of pathogens. Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever in humans. Because mice are not permissive to S. Typhi infection, we employed a murine model of typhoid using S. enterica serovar Typhimurium expressing the Vi polysaccharide (ViPS) of S. Typhi (S. Typhimurium strain RC60) to evaluate the role of natural IgM in pathogenesis. We found that natural mouse IgM binds to S. Typhi and S. Typhimurium. The severity of S. Typhimurium infection in mice is dependent on presence of the natural resistance-associated macrophage protein 1 (Nramp1) allele; therefore, we infected mice deficient in secreted form of IgM (sIgM) on either a Nramp1-resistant (129S) or -susceptible (C57BL\/6J) background. We found that the lack of natural IgM results in a significantly increased susceptibility and an exaggerated liver pathology regardless of the route of infection or the Nramp1 allele. Reconstitution of sIgM\u2212\/\u2212 mice with normal mouse serum or purified polyclonal IgM restored the resistance to that of sIgM+\/+ mice. Furthermore, immunization of sIgM\u2212\/\u2212 mice with heat-killed S. Typhi induced a significantly reduced anti-ViPS IgG and complement-dependent bactericidal activity against S. Typhi in vitro, compared with that of sIgM+\/+ mice. These findings indicate that natural IgM is an important factor in reducing the typhoid severity and inducing an optimal anti-ViPS IgG response to vaccination.<\/jats:p>","DOI":"10.4049\/immunohorizons.2200088","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T05:04:51Z","timestamp":1672722291000},"page":"807-816","source":"Crossref","is-referenced-by-count":7,"title":["The Lack of Natural IgM Increases Susceptibility and Impairs Anti-Vi Polysaccharide IgG Responses in a Mouse Model of Typhoid"],"prefix":"10.1093","volume":"6","author":[{"given":"Akhil S","family":"Alugupalli","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA"},{"name":"Department of Microbiology, University of Pennsylvania School of Veterinary Medicine , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P","family":"Cravens","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin A","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8157-3967","authenticated-orcid":false,"given":"Dania","family":"Gulandijany","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S","family":"Dickinson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4208-7362","authenticated-orcid":false,"given":"Gudrun F","family":"Debes","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5540-2969","authenticated-orcid":false,"given":"Dieter M","family":"Schifferli","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Pennsylvania School of Veterinary Medicine , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas J","family":"B\u00e4umler","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis , Davis, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishore R","family":"Alugupalli","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, PA"},{"name":"Sidney Kimmel Cancer Center, Thomas Jefferson University , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"2025010703535609000_r1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1086\/649541","article-title":"Global trends in typhoid and paratyphoid Fever","volume":"50","author":"Crump","year":"2010","journal-title":"Clin. 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