Autoimmune-prone lpr mice exhibit a prolonged but lethal infection with an attenuated Salmonella Typhimurium strain

Rananaware, SR and Pathak, S and Chakraborty, S and Bisen, RY and Chattopadhyay, A and Nandi, D (2021) Autoimmune-prone lpr mice exhibit a prolonged but lethal infection with an attenuated Salmonella Typhimurium strain. In: Microbial Pathogenesis, 150 .

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Abstract

Autoimmunity can potentially pre-dispose to, exacerbate or ameliorate pathogenic infections. The current study was designed to compare and understand the infection outcomes with Salmonella enterica serovar Typhimurium ATCC 14028s (S. Typhimurium) wild type (WT) and attenuated �rpoS strains, in autoimmune-prone lpr mice. C57BL/6 (B6) and B6/lpr (lpr) 6�8 weeks old mice were orally infected with S. Typhimurium WT and �rpoS strains. Disease outcomes were assessed with respect to survival, organ bacterial load, tissue damage and inflammation in infected mice. The acute infection stage (day 4) was examined and compared to the later stages (up to day 12) post �rpoS infection. S. Typhimurium WT exhibited an acute and lethal infection in both B6 and lpr mice. However, the �rpoS strain exhibited prolonged infection with reduced mortality in B6 mice but complete mortality in lpr mice. During late infection, bacterial load and serum IFNγ levels were higher in the �rpoS strain infected lpr mice compared to B6 mice. The �rpoS strain infected lpr mice also exhibited greater bacterial faecal shedding and greater tissue histopathological changes. Interestingly, �rpoS-infected B6 mice displayed minimal microbial load in the brain; however, sustained brain bacterial load was observed in �rpoS-infected lpr mice, corresponding to abnormal gait. Overall, S. Typhimurium �rpoS is competent in establishing infection but compromised in sustaining it. Nonetheless, lpr mice are less efficient in controlling this attenuated infection. The findings from the study demonstrate that genetic pre-disposition to autoimmunity is sufficient for greater host susceptibility to infection by attenuated S. Typhimurium strains. © 2020 Elsevier Ltd

Item Type:	Journal Article
Publication:	Microbial Pathogenesis
Publisher:	Academic Press
Additional Information:	Copyright to this article belongs to Academic Press
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	18 Jan 2021 06:25
Last Modified:	18 Jan 2021 06:25
URI:	http://eprints.iisc.ac.in/id/eprint/67599

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