Disrupted iron metabolism and mortality during co-infection with malaria and an intestinal gram-negative extracellular pathogen

dos Santos, L. I., Torres, T. A., DIniz, S. Q., Gonçalves, R., Caballero-Flores, G., Núñez, G., Gazzinelli, R. T., Maloy, K. J. and Antonelli, L. R. d. V. (2021) Disrupted iron metabolism and mortality during co-infection with malaria and an intestinal gram-negative extracellular pathogen. Cell Reports, 34(2), 108613. (doi: 10.1016/j.celrep.2020.108613) (PMID:33440153) (PMCID:PMC8655499)

[img] Text
227545.pdf - Published Version
Available under License Creative Commons Attribution.

2MB

Abstract

Individuals with malaria exhibit increased morbidity and mortality when infected with Gram-negative (Gr−) bacteria. To explore this experimentally, we performed co-infection of mice with Plasmodium chabaudi and Citrobacter rodentium, an extracellular Gr− bacterial pathogen that infects the large intestine. While single infections are controlled effectively, co-infection results in enhanced virulence that is characterized by prolonged systemic bacterial persistence and high mortality. Mortality in co-infected mice is associated with disrupted iron metabolism, elevated levels of plasma heme, and increased mitochondrial reactive oxygen species (ROS) production by phagocytes. In addition, iron acquisition by the bacterium plays a key role in pathogenesis because co-infection with a mutant C. rodentium strain lacking a critical iron acquisition pathway does not cause mortality. These results indicate that disrupted iron metabolism may drive mortality during co-infection with C. rodentium and P. chabaudi by both altering host immune responses and facilitating bacterial persistence.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maloy, Professor Kevin
Authors: dos Santos, L. I., Torres, T. A., DIniz, S. Q., Gonçalves, R., Caballero-Flores, G., Núñez, G., Gazzinelli, R. T., Maloy, K. J., and Antonelli, L. R. d. V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cell Reports
Publisher:Elsevier (Cell Press)
ISSN:2211-1247
ISSN (Online):2211-1247
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Cell Reports 34(2):108613
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
313264Regulation of intestinal immune homeostasis by NOD-like receptorsKevin MaloyWellcome Trust (WELLCOTR)N/AIII - Immunology