Iron is an essential element for virtually all cell types due to its role in energy metabolism, nucleic acid synthesis and cell proliferation. Nevertheless, if free, iron induces cellular and organ damage through the formation of free radicals. Thus, iron levels must be firmly controlled. During infection, both host and microbe need to access iron and avoid its toxicity. Alterations in serum and cellular iron have been reported as important markers of pathology. In this regard, ferritin, first discovered as an iron storage protein, has emerged as a biomarker not only in iron-related disorders but also in inflammatory diseases, or diseases in which inflammation has a central role such as cancer, neurodegeneration or infection. The basic research on ferritin identification and functions, as well as its role in diseases with an inflammatory component and its potential as a target in host-directed therapies, are the main considerations of this review.
In the mouse, the progression of the Mycobacterium avium infection is highly dependent on the Nramp1 gene. Strains of mice that express the Nramp1D169 allele are highly susceptible to M. avium infections, while Nramp1G169 strains of mice can control them. Recently, the Nramp1 gene has been cloned and characterized as coding a transmembrane protein, probably involved in divalent cation transport. One possible function of this protein could be the transport of iron out of the parasite-harbouring phagosome. Previous work in our lab has shown both in vitro (in macrophage cultures) and in vivo, that the growth rate of M. avium is highly dependent on the amount of iron available in the system. To try to correlate this with the Nramp1 gene function, BALB/c (susceptible) and C.D2 (resistant) congenic mice were treated for 20 days with different doses of iron-dextran, so as to induce different degrees of iron overload, and infected with M. avium 2447. Iron administration increased M. avium growth in infected organs in a dose-dependent manner at the same time as it decreased the difference in mycobacterial growth between the two mouse strains. These results indicate that an excess of iron hampers Nramp1-encoded function, strongly suggesting a direct involvement of the Nramp1-encoded protein in the transport of this cation.
Despite the antimicrobial mechanisms of vertebrate phagocytes, mycobacteria can survive within the phagosomes of these cells. These organisms use various strategies to evade destruction, including inhibition of acidification of the phagosome and inhibition of phagosome-lysosome fusion. In contrast to mycobacteria, Coxiella burnetii, the etiologic agent of Q fever, inhabits a spacious acidified intracellular vacuole which is prone to fusion with other vacuoles of the host cell, including phagosomes containing mycobacteria. The Coxiella-infected cell thus provides a unique model for investigating the survival of mycobacteria in an acidified phagosome-like compartment. In the present study, murine bone marrow-derived macrophages were infected with eitherMycobacterium avium or Mycobacterium tuberculosis and then coinfected with C. burnetii. We observed that the majority of phagocytosed mycobacteria colocalized to the C. burnetii-containing vacuole, which maintained its acidic properties. In coinfected macrophages, the growth of M. avium was not impaired following fusion with the acidified vacuole. In contrast, the growth rate of M. tuberculosiswas reduced in acidified vacuoles. These results suggest that although both species of mycobacteria inhibit phagosome-lysosome fusion, they may be differentially susceptible to the toxic effects of the acidic environment in the mature phagolysosome.
BackgroundGiardia duodenalis is a widespread parasite of mammalian species, including humans. The prevalence of this parasite in children residing in Portugal is currently unknown. This study intended to estimate G. duodenalis infection prevalence and identify possible associated risk factors in a healthy paediatric population living in the District of the Portuguese capital, Lisbon.MethodsBetween February 2002 and October 2008, 844 children were randomly selected at healthcare centres while attending the national vaccination program. A stool sample and a questionnaire with socio-demographic data were collected from each child. Giardia infection was diagnosed by direct examination of stools and antigen detection by ELISA.ResultsThe population studied revealed a gender distribution of 52.8% male and 47.2% female. Age distribution was 47.4% between 0-5 years and 52.6% between 6-15 years.The prevalence of Giardia infection was 1.9% (16/844) when estimated by direct examination and increased to 6.8% (57/844) when ELISA results were added. The prevalence was higher among children aged 0-5 years (7.8%), than among older children (5.8%), and was similar among genders (6.9% in boys and 6.5% in girls). The following population-variables were shown to be associated risk factors for G. duodenalis infection: mother's educational level (odds ratio (OR)= 4.49; confidence interval (CI): 1.20-16.84), father's educational level (OR = 12.26; CI: 4.08-36.82), presence of Helicobacter pylori infection (OR = 1.82; CI: 1.05-3.15), living in houses with own drainage system (OR = 0.10; CI: 0.02-0.64) and reported household pet contact, especially with dogs (OR = 0.53; CI: 0.31-0.93).ConclusionThe prevalence of giardiasis in asymptomatic children residing in the region of Lisbon is high. Several risk factors were associated with Giardia prevalence and highlight the importance of parents' education and sanitation conditions in the children's well being. The association between G. duodenalis and H. pylori seems an important issue deserving further investigation in order to promote prevention or treatment strategies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.