Dept. of Applied Medicine, Institute of Medical Sciences, University

							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.