Chlamydia pneumoniae: An Etiologic Agent for Late-Onset Dementia

The disease known as late-onset Alzheimer\u27s disease is a neurodegenerative condition recognized as the single most common form of senile dementia. The condition is sporadic and has been attributed to neuronal damage and loss, both of which have been linked to the accumulation of protein deposits in the brain. Significant progress has been made over the past two decades regarding our overall understanding of the apparently pathogenic entities that arise in the affected brain, both for early-onset disease, which constitutes approximately 5% of all cases, as well as late-onset disease, which constitutes the remainder of cases. Observable neuropathology includes: neurofibrillary tangles, neuropil threads, neuritic senile plaques and often deposits of amyloid around the cerebrovasculature. Although many studies have provided a relatively detailed knowledge of these putatively pathogenic entities, understanding of the events that initiate and support the biological processes generating them and the subsequent observable neuropathology and neurodegeneration remain limited. This is especially true in the case of late-onset disease. Although early-onset Alzheimer\u27s disease has been shown conclusively to have genetic roots, the detailed etiologic initiation of late-onset disease without such genetic origins has remained elusive. Over the last 15 years, current and ongoing work has implicated infection in the etiology and pathogenesis of late-onset dementia. Infectious agents reported to be associated with disease initiation are various, including several viruses and pathogenic bacterial species. We have reported extensively regarding an association between late-onset disease and infection with the intracellular bacterial pathoge

Human chlamydial infections: persistence, prevalence, and outlook for the future

Infectious diseases have imposed a profound burden on mankind throughout the history of our species. Importantly, many of the microbe-induced diseases that have plagued us for millennia remain of significant concern in industrialized nations, developing nations, or both, including tuberculosis, cholera, and others. Bacterial pathogens of the Order Chlamydiales have caused disease in both humans and domestic animals for thousands of years, but it is only recently that we have begun to fully understand the subtle and complex long-term consequences of human chlamydial infections. In this article, we describe the current understanding of the biology and pathobiology of the human pathogens Chlamydia trachomatis and C. pneumoniae. We discuss the acute diseases that these important organisms cause, and more importantly, we describe the known and suspected chronic disease sequelae that follow those primary infections. Finally, we explore the economic, social, and human consequences of chlamydial infections, and we propose strategies for ameliorating or obviating those consequences

Protective immunity to chlamydial genital infection: evidence from animal studies

In all animal models for chlamydial infection, there is strong evidence for immunity to reinfection; however, immunity is only complete (ie, preventing infection) in the short term. In the long term, animals are only partially immune (ie, they can be reinfected, but infections are usually abbreviated and less intense than the primary infection). This review will target the mechanisms responsible for long-term versus short-term immunity and explore the roles of various components of the host response in immunity to chlamydial genital infection. An important question about the natural history of Chlamydia trachomatis genital infection, with implications for both chlamydia control programs and vaccine development, is whether immunity to reinfection develops naturally; if so, how long does that immunity last after a natural infection, what are the effector mechanisms, and are there any confounding issues, such as an enhanced pathologic response? If immunity develops, other important considerations for public health programs include how long immunity takes to develop and whether treatment at different times may affect its development. In addition, understanding the various parameters of natural immunity gives us a target to either duplicate or surpass with an appropriate vaccine candidate and immunization regimen. In this section, we will confine our discussion to what has been learned about immunity to reinfection in the 3 major animal models of chlamydial genital tract disease-nonhuman primates, mice, and guinea pigs-and extrapolate t

Microbes and Alzheimer's Disease

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Kinematics of Intracellular Chlamydiae Provide Evidence for Contact-Dependent Development▿ †

A crucial process of chlamydial development involves differentiation of the replicative reticulate body (RB) into the infectious elementary body (EB). We present experimental evidence to provide support for a contact-dependent hypothesis for explaining the trigger involved in differentiation. We recorded live-imaging of Chlamydia trachomatis-infected McCoy cells at key times during development and tracked the temporospatial trajectories of individual chlamydial particles. We found that movement of the particles is related to development. Early to mid-developmental stages involved slight wobbling of RBs. The average speed of particles increased sharply at 24 h postinfection (after the estimated onset of RB to EB differentiation). We also investigated a penicillin-supplemented culture containing EBs, RBs, and aberrantly enlarged, stressed chlamydiae. Near-immobile enlarged particles are consistent with their continued tethering to the chlamydial inclusion membrane (CIM). We found a significantly negative, nonlinear association between speed and size/type of particles, providing further support for the hypothesis that particles become untethered near the onset of RB to EB differentiation. This study establishes the relationship between the motion properties of the chlamydiae and developmental stages, whereby wobbling RBs gradually lose contact with the CIM, and RB detachment from the CIM is coincidental with the onset of late differentiation