Low iron availability modulates the course ofChlamydia pneumoniaeinfection

Abstract

SummaryChlamydiae are obligate intracellular bacteria residing exclusively in host cell vesicles termed inclusions. We have investigated the effects of deferoxamine mesylate (DAM)-induced iron deficiency on the growth of Chlamydia pneumoniae and Chlamydia trachomatis serovar L2. In epithelial cells subjected to iron starvation and infected with either C. pneumoniae or C. trachomatis L2, small inclusions were formed, and the infectivity of chlamydial progeny was impaired. Moreover, for C. trachomatis L2, we observed a delay in homotypic fusion of inclusions. The inhibitory effects of DAM were reversed by adding exogenous iron-saturated transferrin, which restored the production of infectious chlamydiae. Electron microscopy examination of iron-deprived specimens revealed that the small inclusions contained reduced numbers of C. pneumoniae that were mostly reticulate bodies. We have previously reported specific accumulation of transferrin receptors (TfRs) around C. pneumoniae inclusions within cells grown under normal conditions. Using confocal and electron microscopy, we show here a remarkable increase in the amount of TfRs surrounding the inclusions in iron-starved cultures. It has been shown that iron is an essential factor in the growth and survival of C. trachomatis. Here, we postulate that, for C. pneumoniae also, iron is an indispensable element and that Chlamydia may use iron transport pathways of the host by attracting TfR to the phagosome.

Consequences of iron depletion on health in menstruating women

“…In the literature, the relation between infections and the iron status is very controversial. Some in vitro studies demonstrated that iron deficiency inhibited bacterial proliferation, whereas others indicate that this effect is balanced by numerous alterations of the immune system induced by iron deficiency, such as a decrease in delayed hypersensitivity through abnormalities in lymphocyte transformation, and functional abnormalities of the polymorphonuclear leukocytes (Dallman, 1987;Hallberg & Asp, 1996;Walter et al, 1997;Al-Younes et al, 2001). However, the latter studies investigated iron deficiency with anemia.…”

Correction: Genome Watch: Enemies within

“…Blocking iron uptake by infected cells inhibits the growth of these pathogens [29][30][31][32][33] . To access host-derived iron sources, these bacteria exploit specific intracellular niches in the host cell.…”

Interactions between Infections, Nutrients and Xenobiotics

“…Bacterial infection (S. enteritidis) increases cytokine mRNA levels in enterocyte-like Caco-2 human intestinal cells, an increase that was further enhanced with higher Fe concentration (Foster et al, 2001). An elevated Fe status is known to increase the susceptibility to various infections (Al-Younes et al, 2001;Foster et al, 2001;Lounis et al, 2001;Weinberg, 1999;Weiss, 2002). Moreover, Fe accumulation in the liver in human hepatitis C virus infection is associated with an impaired response to IFNα therapy and with faster progression of the disease (Weiss, 2002).…”

“…Results indicate, however, that C. pneumoniae is dependent on Fe for its growth (Al-Younes et al, 2001;Freidank et al, 2001), and that a greater availability of Fe increases the virulence of S. enteritidis bacteria (Foster et al, 2001) and stimulates the growth of M. tuberculosis (Serafin-Lopez et al, 2004). From data in S. enteritis infected Caco-2 cells it has been suggested that an elevated enterocyte Fe status increases the susceptibility to infection and exacerbates the mucosal inflammatory response because of increased cytokine expression (Foster et al, 2001).…”

“…All changes in trace elements, however, may not be favourable for the host (Weiss, 2002), such as the progressive increase of Fe in the brain during scrapie infection in mice (Kim et al, 2000) and in HIV infection in man (Boelaert et al, 1996). Furthermore, many bacteria need Fe for their growth and multiplication and excessive Fe in specific tissues has been shown to promote bacterial infection in those tissues (Al-Younes et al, 2001;Foster et al, 2001;Lounis et al, 2001;Weiss, 2002). Even some neoplasias, cardiomyopathies, and neurodegenerative disorders have been associated with increased levels of Fe (Ke and Qian, 2003;Nystrom-Rosander et al, 2003;Sullivan and Weinberg, 1999;Weinberg, 1999).…”