Abstract

Human zinc deficiency increases susceptibility to bacterial infection. Although zinc supplementation therapies can reduce the impact of disease, the molecular basis for protection remains unclear. Streptococcus pneumoniae is a major cause of bacterial pneumonia, which is prevalent in regions of zinc deficiency. We report that dietary zinc levels dictate the outcome of S. pneumoniae infection in a murine model. Dietary zinc restriction impacts murine tissue zinc levels with distribution post-infection altered, and S. pneumoniae virulence and infection enhanced. Although the activation and infiltration of murine phagocytic cells was not affected by zinc restriction, their efficacy of bacterial control was compromised. S. pneumoniae was shown to be highly sensitive to zinc intoxication, with this process impaired in zinc restricted mice and isolated phagocytic cells. Collectively, these data show how dietary zinc deficiency increases sensitivity to S. pneumoniae infection while revealing a role for zinc as a component of host antimicrobial defences.

Highlights

  • Zinc (Zn) is the second most abundant transition metal ion in humans and has crucial importance in immune function [1]

  • We show that dietary zinc deficiency impacts host tissue zinc abundances and its mobilization during infection by the major respiratory pathogen Streptococcus pneumoniae

  • This study reveals the link between dietary Zn intake and host resistance to bacterial pneumonia, demonstrating the antimicrobial activity of Zn in host niches against invading S. pneumoniae and in potentiating the efficacy of phagocytic cell killing of the pathogen

Read more

Summary

Introduction

Zinc (Zn) is the second most abundant transition metal ion in humans and has crucial importance in immune function [1]. The impact on human health accounts for ~1.4% of annual global mortalities, manifesting in a variety of adverse clinical outcomes including compromised immune defence and an increased susceptibility to infections [3,4,5]. Bacterial diseases associated with Zn deficiency are typically caused by respiratory or enteric pathogens, resulting in pneumonia or diarrhoea, respectively [6, 7]. Clinical trials of Zn supplementation therapies have shown that the morbidity and mortality of pneumonia and diarrhoea can be significantly reduced [7,8,9,10]. The efficacy of Zn supplementation strategies varies, highlighting the fact that the mechanism by which Zn contributes to resistance against bacterial infections remains unclear

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call