M. Di Pietro

Chlamydia pneumoniae and atherosclerosis: current state and future prospectives.

Chlamydia pneumoniae, an intracellular bacterial pathogen, is known as a leading cause of human respiratory tract infections worldwide. Over the last decade, several reports in the literature have suggested that infection with C. pneumoniae may contribute to the pathogenesis of atherosclerosis. In order to play a causative role in chronic disease, C. pneumoniae would need to persist within infected tissue for extended periods of time, thereby stimulating a chronic inflammatory response. C. pneumoniae has been shown to disseminate systemically from the lungs through infected peripheral blood mononuclear cells and to localize in arteries where it may infect endothelial cells, vascular smooth muscle cells, monocytes/macrophages and promote inflammatory atherogenous process. The involvement of C. pneumoniae in atherosclerosis was investigated by seroepidemiological and pathological studies, in vivo and in vitro studies, and in clinical antibiotic treatment trials. This review will provide an update on the role of C. pneumoniae in atherosclerosis focusing on the recent insights and suggesting areas for future research.

Chlamydia pneumoniae induces T cell apoptosis through glutathione redox imbalance and secretion of TNF-α

Chlamydia pneumoniae persistent infection has been implicated in the pathogenesis of several chronic inflammatory diseases including atherosclerosis, and we hypothesized that modulation of the apoptosis of macrophages and/or T cells by C. pneumoniae infection may contribute to the development of such diseases. We therefore evaluated apoptosis, cytokine response, and redox status in human primary T cells and macrophages infected with C. pneumoniae. In addition, co-cultures of T cells and macrophages infected with C. pneumoniae were also carried out. Apoptosis, and levels of glutathione (GSH), glutathione disulfide (GSSG), and tumour necrosis factor (TNF)-α were measured by flow cytometry, high performance liquid chromatography and enzyme-linked immunosorbent assay. C. pneumoniae induced apoptosis in T cells as well as in co-cultures of T cells and infected macrophages by marked decrease in GSH/GSSG ratio and increased production of TNF-α, respectively. The results demonstrate that interaction of C. pneumoniae with T cells and/or macrophages characterized by interference with redox status, and secretion of tumour necrosis factor TNF-α culminates in the induction of T cell apoptosis and survival of infected macrophages. In conclusion, the inappropriate T cell response against C. pneumoniae and survival of infected macrophages could explain the persistence of this intracellular obligate pathogen in the host-organism; it may contribute to the development of chronic inflammatory diseases, although further studies are needed to clarify such a complex mechanism.

Chlamydia pneumoniae and chronic diseases with a great impact on public health.

Chlamydia pneumoniae is recognised as a common cause of respiratory tract infections and has recently been implicated in several extrapulmonary chronic diseases, with great impact on public health, such as atherosclerosis, multiple sclerosis and Alzheimers disease. The involvement of C. pneumoniae in such diseases may be correlated to characteristic features of this pathogen, including intracellular growth and ability to induce persistent forms. C. pneumoniae persistent forms are inherently more suited to evade the host immune response and are more difficult to eradicate by antibiotics. Our preliminary experimental findings show that interaction of C. pneumoniae with macrophages and/or T cells characterized by interference with TNF-α production, and redox state, culminates in the induction of T cell apoptosis and survival of infected macrophages. Based on our evidence, the poor cooperation between T cells and macrophages could lead to an inappropriate immune response against C. pneumoniae that may therefore promote the development of extrapulmonary chronic diseases.

The Elusive but Pathogenic Peptidoglycan of Chlamydiae

Chlamydia species cause a broad spectrum of diseases in humans including severe chronic sequelae related to persistent forms. Despite the lack of detectable amounts of peptidoglycan, several studies suggest the presence of small quantities of peptidoglycan or its derivative at least in some stages of the growth cycle. Based on recent discovery in Chlamydiae of the aminotransferase pathway for biosynthesis of meso-diaminopimelic acid, we demonstrated the up-regulation of the gene (cp0259) encoding L,L-diaminopimelate aminotransferase in chlamydial persistent forms. This finding may be important in the search for target molecules to diagnose and treat Chlamydia-associated chronic diseases.

Cutaneous Infection of Nocardia Altamirensis: The First Case Report

We report the first case of Nocardia altamirensis cutaneous infection in an immunocompetent host. A 53-year-old male, with no predisposing factors, presented with a suppurative papular nodule on the dorsum of his left foot. N. altamirensis was identified by sequencing the 16S ribosomal RNA (rRNA), and treatment with amikacin led to complete resolution of the clinical picture. We believe that cutaneous nocardiosis should be kept in mind as a possible cause of serious complications also in immunocompetent hosts considering a nonspecific clinical picture and misdiagnosis of the infection as well as the poor response to empirical antimicrobial therapy.

Could Chlamydia Pneumoniae Be Considered an Infectious Risk Factor for Inflammatory Diseases Such as Atherosclerosis

Chlamydia pneumoniae, a Gram-negative intracellular obligate bacteria, is recognised as a common cause of upper respiratory tract infections, and accounts for ∼10% of community-acquired pneumonia. In recent years, chronic and persistent infection with C. pneumoniae has been implicated in the pathogenesis of atherosclerosis. Atherosclerosis is regarded as a chronic inflammatory disease that results from complex interactions between a variety of cell types such as endothelial cells, vascular smooth muscle cells, monocytes/macrophages and inflammatory mediators. Involvement of C. pneumoniae in the pathogenesis of atherosclerosis has been supported by findings from seroepidemiologic studies, direct detection of chlamydial DNA, experimental animal and in vitro studies, and antibiotic intervention trials. The spectrum of cell biological, animal, and human clinical data suggests that C. pneumoniae may be considered an infectious risk factor for atherosclerosis but further studies are needed to clarify the etiopathogenetic role of C. pneumoniae in atherosclerotic vessel walls.