Atherosclerotic cardiovascular diseases, chronic inflam-matory diseases of multifactorial etiology, are the lead-ing cause of death worldwide. In the last decade, more infectious agents, labeled as "infectious bu...Atherosclerotic cardiovascular diseases, chronic inflam-matory diseases of multifactorial etiology, are the lead-ing cause of death worldwide. In the last decade, more infectious agents, labeled as "infectious burden", rather than any single pathogen, have been showed to con-tribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae(C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet ag-gregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule produc-tion. Others, such as Helicobacter pylori(H. pylori), in-fluenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall(e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents(such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclero-sis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may con-tribute to atherosclerosis, defining the interplay of moreinfectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be ampli-fied. Clearly, continued research and a greater aware-ness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis.展开更多
The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopo...The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopolysaccharide(LPS) levels, which are used as an indicator of microbial translocation(MT), are elevated throughout the acute and chronic phases of HIV-1 disease. The translocation of bacterial products through the damaged gastrointestinal barrier into the systemic circulation has been described as a driver of immune activation. In contrast, comorbidities that are associated with HIV-1 infection have been attributed to chronic inflammation and immune system dysfunction secondary to MT or low-level HIV-1 replication in plasma and cell reservoirs. Moreover, accelerated aging is significantly associated with chronic inflammation, immune activation, and immune senescence. In this review, we aimed to investigate the role of inflammation as a pivotal marker in the pathogenesis of HIV-1 disease. We will discuss the key features of chronic inflammation and immune activation that are observed during the natural course of the disease and those features that are detected in c ART-modified infection. The review will focus on the following aspects of HIV-1 infection:(1) MT;(2) the role of residual viremia; and(3) "immune senescence" or "inflammaging." Many questions remain unanswered about the potential mechanisms that are involved in HIV-1 pathogenesis. Further studies are needed to better investigate the mechanisms that underlie immune activation and their correlation with HIV-1 disease progression.展开更多
基金Supported by Grants to R.Sessa from Center for Social Disease Research,"Sapienza"University,Rome
文摘Atherosclerotic cardiovascular diseases, chronic inflam-matory diseases of multifactorial etiology, are the lead-ing cause of death worldwide. In the last decade, more infectious agents, labeled as "infectious burden", rather than any single pathogen, have been showed to con-tribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae(C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet ag-gregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule produc-tion. Others, such as Helicobacter pylori(H. pylori), in-fluenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall(e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents(such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclero-sis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may con-tribute to atherosclerosis, defining the interplay of moreinfectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be ampli-fied. Clearly, continued research and a greater aware-ness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis.
文摘The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopolysaccharide(LPS) levels, which are used as an indicator of microbial translocation(MT), are elevated throughout the acute and chronic phases of HIV-1 disease. The translocation of bacterial products through the damaged gastrointestinal barrier into the systemic circulation has been described as a driver of immune activation. In contrast, comorbidities that are associated with HIV-1 infection have been attributed to chronic inflammation and immune system dysfunction secondary to MT or low-level HIV-1 replication in plasma and cell reservoirs. Moreover, accelerated aging is significantly associated with chronic inflammation, immune activation, and immune senescence. In this review, we aimed to investigate the role of inflammation as a pivotal marker in the pathogenesis of HIV-1 disease. We will discuss the key features of chronic inflammation and immune activation that are observed during the natural course of the disease and those features that are detected in c ART-modified infection. The review will focus on the following aspects of HIV-1 infection:(1) MT;(2) the role of residual viremia; and(3) "immune senescence" or "inflammaging." Many questions remain unanswered about the potential mechanisms that are involved in HIV-1 pathogenesis. Further studies are needed to better investigate the mechanisms that underlie immune activation and their correlation with HIV-1 disease progression.
