Postdoctoral Fellow, Monash University
Uncovering a new mechanism for immune cell development
The immune system is comprised of a wide range of cells which are essential for combating the invasion of pathogens we encounter daily. Recently a number of 'non-classical' immune cells have been uncovered and, surprisingly, have been found to have an enormous impact on the host's ability to combat disease and cancer. One such cell is termed the gamma delta T cell, and present at highest abundance in the intestine and the liver where the natural, healthy bacteria are at the highest levels. These gamma delta T cells have been proposed to have an inhibitory effect on the immune system, so to not kill off the bacteria present in the gut. These gut bacteria have been attributed to maintaining a normal, functioning immune system, and the loss or abnormal distribution of these cells have been attributed to obesity, gastrointestinal disorders and global metabolism disorders. Therefore, without the inhibitory effects of these gamma delta T cells, the host would face a wide range of diseases and possibly an early death. My research has uncovered a completely new way for the gamma delta cells to develop and mature. The development of these cells is not well understood, so with the results of my research, we can now look into driving the development of these cells in people experiencing metabolic disorders, potentially now having a way to combat obesity and intestinal disorders which have a major impact on the health industry and general health.
Abstract: Mammals and their intestinal microbiota peacefully coexist in a mutualistic relationship. Commensal bacteria play an active role in shaping and modulating physiological processes in the host, which include, but are not restricted to, the immune system and the intestinal barrier. Both play a crucial role in containing intestinal bacteria and other potentially noxious luminal antigens within the lumen and mucosal compartment. Although mutualism defines the relationship between the host and the intestinal microbiota, disruptions in this equilibrium may promote disease. Thus, alterations in gut microbiota (dysbiosis) have been linked to the recent increased expression of obesity, allergy, autoimmunity, functional and inflammatory disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). In this article, we review the evidence supporting a role of gut microbiota in regulating intestinal barrier function. We discuss the hypothesis that microbial factors can modulate the barrier in ways that can prevent or promote gastrointestinal disease. A better understanding of the role of the intestinal microbiota in maintaining a functional intestinal barrier may help develop targeted strategies to prevent and treat disease.
Pub.: 24 Oct '12, Pinned: 28 Aug '17
Abstract: Many immune-based intestinal disorders, such as ulcerative colitis and Crohn's disease, as well as other illnesses, may have the intestines as an initial cause or aggravator in the development of diseases, even apparently not correlating directly to the intestine. Diabetes, obesity, multiple sclerosis, depression, and anxiety are examples of other illnesses discussed in the literature. In parallel, importance of the gut microbiota in intestinal homeostasis and immunologic conflict between tolerance towards commensal microorganisms and combat of pathogens is well known. Recent researches show that the immune system, when altered by the gut microbiota, influences the state in which these diseases are presented in the patient directly and indirectly. At the present moment, a considerable number of investigations about this subject have been performed and published. However, due to difficulties on correlating information, several speculations and hypotheses are generated. Thus, the present review aims at bringing together how these interactions work-gut microbiota, immune system, and their influence in the neuroimmune system.
Pub.: 12 Mar '15, Pinned: 28 Aug '17
Abstract: All higher organisms negotiate a truce with their commensal microbes and battle pathogenic microbes on a daily basis. Much attention has been given to the role of the innate immune system in controlling intestinal microbes and to the strategies used by intestinal microbes to overcome the host immune response. However, it is becoming increasingly clear that the metabolisms of intestinal microbes and their hosts are linked and that this interaction is equally important for host health and well-being. For instance, an individual's array of commensal microbes can influence their predisposition to chronic metabolic diseases such as diabetes and obesity. A better understanding of host-microbe metabolic interactions is important in defining the molecular bases of these disorders and could potentially lead to new therapeutic avenues. Key advances in this area have been made using Drosophila melanogaster. Here, we review studies that have explored the impact of both commensal and pathogenic intestinal microbes on Drosophila carbohydrate and lipid metabolism. These studies have helped to elucidate the metabolites produced by intestinal microbes, the intestinal receptors that sense these metabolites, and the signaling pathways through which these metabolites manipulate host metabolism. Furthermore, they suggest that targeting microbial metabolism could represent an effective therapeutic strategy for human metabolic diseases and intestinal infection.
Pub.: 05 Mar '16, Pinned: 27 Aug '17
Abstract: Chronic inflammation in adipose tissue, possibly related to adipose cell hypertrophy, hypoxia, and/or intestinal leakage of bacteria and their metabolic products, likely plays a critical role in the development of obesity-associated insulin resistance (IR). Cells of both the innate and adaptive immune system residing in adipose tissues, as well as in the intestine, participate in this process. Thus, M1 macrophages, IFN-γ-secreting Th1 cells, CD8+ T cells, and B cells promote IR, in part through secretion of proinflammatory cytokines. Conversely, eosinophils, Th2 T cells, type 2 innate lymphoid cells, and possibly Foxp3+ Tregs protect against IR through local control of inflammation.
Pub.: 04 Jan '17, Pinned: 27 Aug '17
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