Effects of Zinc Deficiency and Pneumococcal Surface Protein A Immunization on Zinc Status and the Risk of Severe Infection in Mice

Abstract

Streptococcus pneumoniae is a major cause of illness and death in children in developing countries. In these children, zinc deficiency is associated with an increased risk of acute respiratory tract infections, which can be reduced by daily zinc administration. Severe infections decrease zinc levels in plasma and may thereby move individuals with preexisting low zinc stores into a vicious cycle of infection and unavailable zinc. Pneumococcal surface protein A (PspA) has emerged as a promising vaccine candidate, and immunization with this antigen protects animals from pneumococcal infection. In an animal experiment, we measured the effect of zinc depletion on the immune response to parenterally administrated PspA and assessed the effect of this PspA vaccination and zinc depletion on the severity of pneumococcal infection and on zinc status. Mice were kept on different diets for 5 weeks, immunized twice 14 days apart, and challenged intranasally with S. pneumoniae. Mice on the zinc-deficient diet showed substantially reduced immune responses to PspA, more extensive pneumococcal colonization in the nasal mucosa, more severe infections, and an increased risk of death. PspA immunization reduced the risk of severe disease, and the reduction in severity was reflected in substantially reduced zinc depletion from bones.

Zinc Protection against Pneumolysin Toxicity on Rat Cochlear Hair Cells

“…In conclusion, both studies in mice and in children, showing a protective effect of zinc during infections due to S. pneumoniae [Strand et al, 2001[Strand et al, , 2003Kumar et al, 2004;Mahalanabis et al, 2004], agree with our benchside results. Our work directly demonstrates that zinc has a protective effect against PLY toxicity on HCs.…”

“…Studies in mice and in children have linked zinc deficiency with an increased risk of severe pneumococcal infection and reduced immune response to pneumococcal surface proteins [Strand et al, 2001[Strand et al, , 2003Kumar et al, 2004]. Moreover, zinc supplementation can decrease the severity of pneumococcal respiratory infections [Mahalanabis et al, 2004].…”

Lactococcus lactis ZitR Is a Zinc-Responsive Repressor Active in the Presence of Low, Nontoxic Zinc Concentrations In Vivo

“…Zinc exhaustion conditions can often be encountered in hosts, and the induction of Adc uptake systems could favor colonization. An increased risk of acute respiratory tract infections by S. pneumoniae is associated with zinc deficiency in children and can be reduced by zinc administration, and mice kept on a zinc-deficient diet show more extensive pneumococcal colonization in the nasal mucosa (46). Furthermore, as AdcR regulates genes encoding surface-exposed proteins involved in the invasion of Zn(II)-poor tissues (compared to blood), repression of these genes in response to elevated FIG.…”

Opposite Effects of Mn2+and Zn2+on PsaR-Mediated Expression of the Virulence GenespcpA,prtA, andpsaBCAofStreptococcus pneumoniae

“…Zn 2ϩ levels are elevated during inflammation (53), and Zn 2ϩ administration reduces airway infections in children in developing countries (71). Moreover, Zn 2ϩ deficiency results in an increased risk of pneumococcal infection and death in mice (75) and in a lower immune response to the pneumococcal antigen PspA (76). Interestingly, several studies suggest that the use of and response to metal ions, such as Zn , is important for the virulence and physiology of pathogenic streptococci (3,11,12,18,30,32,39,40,46,50,54,55,63,64,66,67).…”