NRI 2006

NRI 2006 - Nature Reviews Immunology | AOP, published...

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The study of pathogenic microorganisms and the host response to infection has been central to the fields of microbiology and immunology for more than a cen- tury 1 . The research of microbiologists Louis Pasteur and Robert Koch was driven by the goal of identifying the microbial agents that cause infections in humans. One hundred years after Koch received the Nobel Prize for the discovery of the aetiological mediator of tuber culosis, J. Robin Warren and Barry Marshall were awarded the Nobel Prize in Physiology or Medicine 2005 for their work on the pathogenic bacterium Helicobacter pylori , the causative agent of many gastric ulcers. Furthermore, ~30 Nobel Prizes have been awarded for work related to immunology. As a result of some of these studies, numer- ous molecular and cellular inflammatory responses to bac- terial virulence factors are now well documented 2 . From this information, it is evident that scientific investigations have been overwhelmingly focused on microbial patho- genesis and on immune responses to pathogens. However, bac terial infections are relatively rare and opportunistic, and most human encounters with bacteria involve benign micro organisms that are found in the environment or commensal microorganisms that live in the gut 3–6 . These commensal microorganisms are the species with which we have co-evolved. It now seems that commensal microorganisms, unlike pathogens, might have a role in our development, physiological function and health. All mammals are born sterile and are colonized subsequently by microorganisms 7 . Nearly every sur- face of mammals that is exposed to the environment is inhabited by commensal bacteria. There is no better example of such a surface than the lower gastro intestinal tract, which contains an astounding number of bac- teria 8,9 . How — and, more importantly, why — does this immunocompetent environment allow these micro- organisms to coexist in such high numbers? And what distinguishes these permanent and benign members of the gut microflora from pathogenic bacteria that induce inflammation? Recently, researchers have proposed that commensal bacteria have evolved in ways that improve the health of their hosts, and several microorganisms are being investigated for their beneficial potential: for example, as probiotics 10–15 . It has recently been reported that an immunomodu- latory molecule that is expressed by commensal bacteria is involved in directing the development of a normal mammalian immune system 16 . Bacteroides fragilis pro- duces a zwitterionic polysaccharide (ZPS) that activates CD4 + T cells and can correct certain immune defects, such as the reduced proportion of CD4 + T cells in the splenic lymphocyte population and the dysregulated sys- temic cytokine production that are found in the absence of bacterial colonization. So, in contrast to the virulence factors of pathogenic bacteria, which induce disease, the ZPSs of symbiotic bacteria have emerged as the archetypal members of a family of health-promoting microbial molecules known as symbiosis factors. Commensal bac-
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This note was uploaded on 11/20/2009 for the course BI 2 taught by Professor Elowitz,m during the Fall '08 term at Caltech.

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NRI 2006 - Nature Reviews Immunology | AOP, published...

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