16 Dec How Does Candida Elude the Immune System?
MedicalResearch.com Interview with:
Professor Alistair J P Brown DSc FSB FAAM FRSE
Aberdeen Fungal Group, MRC Centre for Medical Mycology,
University of Aberdeen, Institute of Medical Sciences,
Foresterhill, Aberdeen UK
MedicalResearch.com: What is the background for this study?
Response: Most of us harbor the yeast Candida albicans, and most of the time it does us no harm. However, under certain circumstances it can break out to cause nasty infections of the mouth or genitalia (thrush), or potentially fatal infections in vulnerable intensive care patients. Indeed, over half of women will suffer at least one episode of vulvovaginal candidiasis in their lifetime, and over 5% of women suffer recurrent episodes (four or more episodes per annum). Also, it has been estimated that there are over 400,000 life-threatening systemic Candida infections worldwide per annum, of which over 40% are fatal (see Science Translational Medicine (2012) vol. 4, 165rv13). A key to this is the potency of our immunological defenses: the weaker our defenses the more vulnerable we are to fungal infection. Therefore, we in the Medical Research Council (MRC) Centre for Medical Mycology – and other groups worldwide – are studying the mechanisms by which our immune cells recognize and kill invading Candida cells, thereby protecting us from infection.
MedicalResearch.com: What are the main findings?
Response: In this study, which was funded by the European Research Council and the MRC, our team has discovered that Candida albicans is actually a “moving target” for our immune defenses. We have discovered that this fungus responds to a natural chemical in our bodies (lactic acid) by altering its cell surface, thereby making it more difficult for our immune cells to detect it. As a result, fewer immune cells are recruited to an infection site, and the fungus is better able to cause disease. In this paper we have defined key molecular mechanisms that mediate this process and hence drive this “moving target”.
MedicalResearch.com: What should readers take away from your report?
Response: Our study has not made Candida more dangerous. Rather we have learned something new, fundamental and interesting about the way this fungus behaves inside us. The fact that Candida is a moving target makes it more difficult for our immune defenses to deal with it. For healthy individuals this is not an issue because their immune systems are potent. However, for vulnerable patients with weakened immune systems, this moving target might contribute to their vulnerability.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: With the support of the MRC and with help from our collaborators in the Netherlands, we are continuing to characterize “the moving target”. We have identified other host signals that trigger the moving target (i.e. cause Candida to alter its cell surface, and hence affect its recognition by immune cells). We are defining the molecular events that activate these cell surface changes, and whether these changes can be blocked to stop the moving target. This is because, in principle, if the moving target can be stopped, this would help a weakened immune system recognize the invading fungus and kill it. A therapy based on this principle could conceivably complement our current armory of antifungal drugs.
MedicalResearch.com: Is there anything else you would like to add?
Response: This is fundamental science that provides insight into how a pathogenic fungus behaves. It will take time to translate these findings to the clinic. Nevertheless, we strongly believe that fundamental science such as this will make the ultimate goal – the saving of lives – more achievable.
We are very grateful for the funding from the Europe and the UK Research Councils that supported this work, and for the help and advice from our excellent collaborators in Europe, North America and Asia.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Lactate signalling regulates fungal β-glucan masking and immune evasion
Elizabeth R. Ballou, Gabriela M. Avelar, Delma S. Childers, Joanna Mackie, Judith M. Bain, Jeanette Wagener, Stavroula L. Kastora, Mirela D. Panea, Sarah E. Hardison, Louise A. Walker, Lars P. Erwig,Carol A. Munro, Neil A. R. Gow, Gordon D. Brown, Donna M. MacCallum & Alistair J. P. Brown
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