An exaggerated immune response in female BALB/c mice controls initial Toxoplasma gondii multiplication but increases mortality and morbidity relative to male mice

Alonaizan, R., Woods, S., Hargrave, K. E. and Roberts, C. W. (2021) An exaggerated immune response in female BALB/c mice controls initial Toxoplasma gondii multiplication but increases mortality and morbidity relative to male mice. Pathogens, 10(9), 1154. (doi: 10.3390/pathogens10091154) (PMID:34578186) (PMCID:PMC8470933)

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Abstract

Studies indicate that female mice are more susceptible to T. gondii infection, as defined by higher mortality rates in comparison to male mice. However, whether this is due to an inability to control initial parasite multiplication or due to detrimental effects of the immune system has not been determined. Therefore, the following studies were undertaken to determine the influence of sex on early parasite multiplication and the immune response during T. gondii infection and to correlate this with disease outcome. Early parasite replication was studied through applying an in vivo imaging system (IVIS) with luciferase expressing T. gondii. In parallel immunological events were studied by cytometric bead array to quantify key immunological mediators. The results confirmed the previous findings that female mice are more susceptible to acute infection, as determined by higher mortality rates and weight loss compared with males. However, conflicting with expectations, female mice had lower parasite burdens during the acute infection than male mice. Female mice also exhibited significantly increased production of Monocyte Chemoattractant Protein-1 (MCP-1), Interferon (IFN)-γ, and Tumour Necrosis Factor (TNF)-α than male mice. MCP-1 was found to be induced by T. gondii in a dose dependent manner suggesting that the observed increased levels detected in female mice was due to a host-mediated sex difference rather than due to parasite load. However, MCP-1 was not affected by physiological concentration of estrogen or testosterone, indicating that MCP-1 differences observed between the sexes in vivo are due to an as yet unidentified intermediary factor that in turn influences MCP-1 levels. These results suggest that a stronger immune response in female mice compared with male mice enhances their ability to control parasite replication but increases their morbidity and mortality.

Item Type:Articles
Keywords:Toxoplasma gondii, sex differences, immune response, IVIS, parasite burdens, MCP-1, immune endocrine.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hargrave, Dr Kerrie
Creator Roles:
Hargrave, K. E.Methodology, Formal analysis, Investigation, Writing – review and editing
Authors: Alonaizan, R., Woods, S., Hargrave, K. E., and Roberts, C. W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Pathogens
Publisher:MDPI
ISSN:2076-0817
ISSN (Online):2076-0817
Published Online:08 September 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Pathogens 10(9): 1154
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.15129/108ef43f-accc-4de5-8a36-edadc5987810

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190659BBSRC Doctoral Training Partnership 2012Jeremy MottramBiotechnology and Biological Sciences Research Council (BBSRC)BB/J013854/1MVLS - Graduate School