Candida and candidiasis in HIV-infected patients: Where commensalism, opportunistic behavior and frank pathogenicity lose their borders
ABSTRACT In this era of efficacious antiretroviral therapy and consequent immune reconstitution, oropharyngeal and esophageal candidiasis (OPC and OEC) still remain two clinically relevant presentations in the global HIV setting. Both diseases are predominantly caused by Candida albicans, a polymorphic fungus which is a commensal microbe in the healthy individual but can become an aggressive pathogen in a debilitated host. Actually, C. albicans commensalism is not the result of a benign behavior of one of the many components of human microbiota, but rather the result of host's potent innate and adaptive immune responses that restrict the growth of a potentially dangerous microrganism on the epithelia. An important asset guarding against the fungus is the Th17 functional subset of T helper cells. The selective loss of these cells with the progression of HIV infection causes the decay of fungal containment on the oral epithelium and allows C. albicans to express its pathogenic potential. An important part of this potential is represented by mechanisms to evade host immunity and enhance inflammation and immunoactivation. In C. albicans, these mechanisms are mostly incorporated into and expressed by characteristic morphogenic transitions such as the yeast-to-hyphal growth and the white-to-opaque switch. In addition, HIV infection generates an 'environment' selecting for overexpression of the virulence potential by the fungus, particularly concerning the secreted aspartyl proteinases (Saps). These enzymes can degrade critical host defense components such as complement and epithelial defensive proteins such as histatin-5 and E-cadherin. It appears that part of this enhanced Candida virulence could be induced by the binding of the fungus to HIV and/or induced by HIV proteins such as GP160 and tat. Both OPC and OEC can be controlled by old and new antimycotics, but in the absence of host collaboration, anticandidal therapy may become ineffective in the long run. For these reasons, new therapeutics targeting virulence factors and specific immune interventions are being addressed. Among these new approaches, vaccination is a promising one. Two subunit vaccines based on antigens dominantly expressed by C. albicans in vivo, that is the Als3 adhesin and Sap2, have recently undergone phase 1 clinical trials. Overall, studies of Candida and candidiasis in the HIV-positive patient while certainly contributing to a more effective control of the microorganism may also provide useful information on HIV-host relationship itself that can assist the fight against the virus.
- SourceAvailable from: Sheila M Keating[Show abstract] [Hide abstract]
ABSTRACT: From early in the HIV epidemic it was appreciated that many inflammatory markers such as neopterin and TNF-α were elevated in patients with AIDS. With the advent of modern technology able to measure a broad array of cytokines, we now know that from the earliest points of infection HIV induces a cytokine storm. This review will focus on how cytokines are disturbed in HIV infection and will explore potential therapeutic uses of cytokines. These factors can be used directly as therapy during HIV infection, either to suppress viral replication or prevent deleterious immune effects of infection, such as CD4+ T cell depletion. Cytokines also show great promise as adjuvants in the development of HIV vaccines, which would be critical for the eventual control of the epidemic.Cytokine & growth factor reviews 06/2012; 23(4-5):193-206. DOI:10.1016/j.cytogfr.2012.05.006 · 6.54 Impact Factor
- Frontiers in Microbiology 12/2013; 4:381. DOI:10.3389/fmicb.2013.00381 · 3.94 Impact Factor
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ABSTRACT: Metagenomics which combines the power of genomics, bioinformatics, and systems biology, provide new access to the microbial world. Metagenomics permit the genetic analysis of complex microbial populations without requiring prior cultivation. Through the conceptual innovations in metagenomics and the improvements in DNA high-throughput sequencing and bioinformatics analysis technology, gastrointestinal microbiology has entered the metagenomics era and become a hot topic worldwide. Human microbiome research is underway, however, most studies in this area have focused on the composition and function of the intestinal microbiota and the relationship between intestinal microbiota and metabolic diseases (obesity, diabetes, metabolic syndrome, etc.) and intestinal disorders [inflammatory bowel disease, colorectal cancer, irritable bowel syndrome (IBS), etc.]. Few investigations on microbiota have been conducted within the upper gastrointestinal tract (esophagus, stomach and duodenum). The upper gastrointestinal microbiota is essential for several gastrointestinal illnesses, including esophagitis, Barrett's esophagus, and esophageal carcinoma, gastritis and gastric cancer, small intestinal bacterial overgrowth, IBS and celiac disease. However, the constitution and diversity of the microbiota in different sections of the upper gastrointestinal tract under health and various disease states, as well as the function of microbiota in the pathogenesis of various digestive diseases are still undefined. The current article provides an overview of the recent findings regarding the relationship between upper gastrointestinal microbiota and gastrointestinal diseases; and discusses the study limitations and future directions of upper gastrointestinal microbiota research.World Journal of Gastroenterology 03/2013; 19(10):1541-50. DOI:10.3748/wjg.v19.i10.1541 · 2.43 Impact Factor