Dept. of Applied Medicine, Institute of Medical Sciences, University
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10.18 Immune responses to Candida albicans are mediated by a balance between Th1, Th17 and Tr1 responses 1 2 1 2 Andrew M. Hall , Donna M. MacCallum , Natasha Whibley , Neil A.R. Gow , Robert N. 1 Barker 1 Dept. of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, 2 Aberdeen. AB25 2ZD, United Kingdom, Dept. of Microbiology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen. AB25 2ZD, United Kingdom There is a need for more specific immunotherapy to treat infections associated with Candida albicans. Despite the development of new antifungal chemotherapy, the incidence rate of candidaemia in humans remains high. Recent reports implicate the newly identified subset of Th17 cells in the development of immune responses to C.albicans, however, little is known about the balance between Th17 cells and the previously identified Th1 and Tr1 responses. Manipulating these responses is likely to be pivotal in the development of more effective immunotherapy. Clinical isolates of C.albicans, taken from the blood of human patients, were found to exhibit different virulence in mice. The aim of this work was to determine whether these strains of C.albicans induce different helper T cell response profiles in Balb/c mice. This work confirms that a strong Th1 response is associated with the less virulent strain (HUN96) and a Th17 response is associated with the more pathogenic C.albicans (SC5314). There was an increase in IL-10 secreting helper T cells isolated from mice infected with the HUN96 strain of C.albicans. Interestingly, IL-17 production was predominantly found in response to a cell wall antigen preparation isolated from the hyphal form of C. albicans. To investigate the antigens involved in the helper T cell response mice were then infected with C.albicans strains deficient in the expression of candidate cell wall proteins. Helper T cell responses from mice infected with a strain lacking hyr1p expression were found to be similar to that of mice infected with the less virulent HUN96 strain, rather than the virulent parent strain. These results suggest that the hyr1p antigen plays an important role in the balance between Th1, Th17 and Tr1 responses that may control the immunopathology associated with Candida albicans infection.