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The immune response to fungal challenge
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
Jeffery Hu, Jeffery J. Auletta
Macrophages are another key effector cell in the defense against fungal infection. They have a particular role in controlling disseminated fungal infection and are recruited to site of infection through chemokine receptors. Polymorphism in genes that decrease CX3C chemokine receptor 1 function found on monocytes revealed increased susceptibility to disseminated infection but not mucosal infection [44,45]. Additionally, deficiency in CC-chemokine receptor 2 in murine models also demonstrated increased susceptibility to disseminated infection. [46]. Monocytes and macrophages play an important role in “innate immunity” or “trained immunity.” This has been demonstrated in studies performed in which mice previously exposed to attenuated strains of C. albicans were protected from invasive candidiasis in subsequent fungal challenge [47]. Such immunity was thought to have been mediated by epigenetic reprogramming of innate immune cells allowing for enhanced production of proinflammatory cytokines [48]. Clinical relevance of trained immunity has been suggested by reports of defective trained immunity in patients with chronic mucocutaneous candidiasis and points to new therapeutic approaches to vaccinations [49].
Coronary Heart Disease Risk Factors
Published in Mark C Houston, The Truth About Heart Disease, 2023
All types of organisms including bacteria, viruses, parasites, tuberculosis, and fungi (commonly called microorganisms) can increase the risk of CHD and MI. This association is true for both active, previous, or inactive infections. This is called the lifetime pathogenic burden of infections. There is clearly a link between infectious burden, history of infections, active infections, and atherosclerosis. The greater the number of microorganisms to which one displays a previous immune experience (reactive T cells or IgG antibody levels), the greater is the CHD. This pathogenic burden of various microorganisms has a significant correlation with endothelial dysfunction, coronary artery spasm, the presence coronary artery plaque and the severity of CHD as defined by coronary artery calcification (CAC) scan and coronary arteriograms. I will now outline the present relationships and findings of all of these infections and the risk of CHD and MI.Individual microorganisms also have significant correlations with CHD, including periodontal microbes, herpes simplex virus (HSV), cytomegalovirus (CMV), H. Pylori, Chlamydia Pneumoniae, Hepatitis A, B, C, HIV, and Epstein Barr virus (EBV), and all bacteria and others as defined by the production of IgG and IgM antibodies. H. pylori-positive patients with endothelial dysfunction (ED) had resolution of the ED after treatment and eradication of the H. pylori infection.The DNA of many viruses and bacteria can be detected in the coronary arteries and in the plaque at autopsy.In the presence of a chronic bacterial infection (periodontal or gum disease being the most common), mononuclear cells, such as T cells, infiltrate the gum tissue, gobble up the corresponding microbes, and digest them. If that mononuclear cell happens to traverse a coronary artery containing an active plaque, it may be nonspecifically pulled into the lesion. There it may display gum microbes which induce inflammation and an immune response that activates the plaque to an unstable form that is prone to rupture.There is a strong association between an acute myocardial infarction and acute bacterial and viral infections. This risk is highest the first few weeks after the infection but remains elevated for a year after severe infection. This is mediated by trained immunity.
Maintaining a ‘fit’ immune system: the role of vaccines
Published in Expert Review of Vaccines, 2023
Béatrice Laupèze, T. Mark Doherty
The clinical implications of ‘trained immunity’ are profound, with potentially far-reaching impacts for disease prevention and treatment. ‘Trained immunity,’ and the modification of initial innate immune responses by preexisting immune responses, could help explain some of the variability observed in the severity of infectious diseases experienced by different individuals. From a clinical perspective, targeted induction of ‘trained immunity’ could be used in to help prevent infections, prevent and treat cancers, and prevent autoimmune or other inflammatory diseases [25–28]. As yet, these opportunities remain largely theoretical, although immune activation using bacteria or bacterial toxins have been used to treat cancer (with variable degrees of success) for over a century [29,30]. The most successful of these therapies uses BCG vaccine to treat urothelial cell cancers and remains in widespread use. The mechanism was initially unknown [5], but is now thought to be due to ‘trained immunity’ rather than BCG antigen-specific immunity [27,31]. On the other hand, caution remains about inducing nonspecific responses by immunotherapy due to the concern that inappropriate activation of ‘trained immunity’ could have adverse effects, potentially contributing to the onset or exacerbation of autoimmune diseases [32].
Chapter 2: Transmission and pathogenesis of tuberculosis
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2022
Richard Long, Maziar Divangahi, Kevin Schwartzman
Contrary to focusing on the adaptive immune response, epidemiological data show that among close household contacts of highly infectious TB patients, up to 50% of exposed individuals do not convert their TST response from negative to positive, suggesting many of these individuals are intrinsically resistant to infection by M. tuberculosis,109,110 These studies support the idea that perhaps the best window of opportunity to eradicate M. tuberculosis is during the early phase of infection, when the bacteria are still in the airway and have not initiated adaptive immunity and granuloma formation. These studies indicate that developing a vaccine targeting innate immunity may prevent TB.111 However, designing such a vaccine will require a better understanding of innate immunity, especially the memory capacity of innate cells. Simple organisms such as plants and invertebrates, which only possess innate immune defenses, have demonstrated immunological memory (ie, the primary exposure to a pathogen resulted in more efficient immunity to a subsequent challenge with the same pathogen).112 Similarly, innate immune cells in vertebrates can generate a memory-like response (termed trained immunity), which is more efficient in preventing subsequent infection by a broad spectrum of pathogens and that is largely driven by epigenetic modifications.113–115 Therefore, identifying the key determinants of trained immunity and their protective function will lead to new targets and vaccine strategies against M. tuberculosis.
Thirty years of recombinant BCG: new trends for a centenary vaccine
Published in Expert Review of Vaccines, 2021
Lazaro M Marques-Neto, Zuzanna Piwowarska, Alex I. Kanno, Luana Moraes, Monalisa M Trentini, Dunia Rodriguez, Jose L. S. C. Silva, Luciana C. C. Leite
Within the innate immune response induced by BCG, the identification of innate immune memory mechanisms, leading to the induction of nonspecific immune responses, has boosted research on BCG. The term ‘trained immunity’ was proposed by Netea et al. (2011) to describe the induction of protection against heterologous infections [19]. BCG immunization results in epigenetic reprogramming of cells of the innate immune system such as monocytes and natural killer cells. This reprogramming is accompanied by metabolic changes in the cells that pre-dispose them to better respond to subsequent encounters with unrelated pathogens/antigens [20]. In this context, a correlation between BCG vaccination and lower COVID-19 morbidity and mortality has stimulated several clinical trials to confirm this effect [21].