The Lack of Natural IgM Increases Susceptibility and Impairs Anti-Vi Polysaccharide IgG Responses in a Mouse Model of Typhoid

Authors

Akhil S. Alugupalli, Thomas Jefferson University
Matthew P. Cravens, Thomas Jefferson University
Justin A. Walker, Thomas Jefferson University
Dania Gulandijany, Thomas Jefferson University Hospital
Gregory S. Dickinson, Thomas Jefferson University
Genevieve Lewis, University of California at Davis
Gudrun F. Debes, Thomas Jefferson University
Dieter M. Schifferli, University of Pennsylvania
Andreas J. Bäumler, University of California at Davis
Kishore R. Alugupalli, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

12-1-2022

Comments

This article is the author's final published version in ImmunoHorizons, Volume 6, Issue 12, December 2022, Pg. 807 - 816.

The published version is available at https://doi.org/10.4049/immunohorizons.2200088. Copyright © 2022 The Authors.

Abstract

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-/- mice with normal mouse serum or purified polyclonal IgM restored the resistance to that of sIgM+/+ mice. Furthermore, immunization of sIgM-/- 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.

Recommended Citation

Alugupalli, Akhil S.; Cravens, Matthew P.; Walker, Justin A.; Gulandijany, Dania; Dickinson, Gregory S.; Lewis, Genevieve; Debes, Gudrun F.; Schifferli, Dieter M.; Bäumler, Andreas J.; and Alugupalli, Kishore R., "The Lack of Natural IgM Increases Susceptibility and Impairs Anti-Vi Polysaccharide IgG Responses in a Mouse Model of Typhoid" (2022). Department of Microbiology and Immunology Faculty Papers. Paper 169.
https://jdc.jefferson.edu/mifp/169

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

36480484

Language

English