Mucosal candidiasis

Name(s) of Coordinator(s)

Flavia de Bernardis –Stavroula Antonopoulou

Objectives

The aim of this project is to extend previous clinical and microbiological investigations and, through international collaborations, to understand host-parasite interactions in candidiasis and try to generate novel efficient therapeutic and/or immunological tools. Particularly, we will try to understand the fungal and host components involved in the pathogenesis of mucosal candidiasis and to assess the protective role of recombinant proteins (Sap2 and mannoprotein) as potential candidate vaccines against mucosal candidiasis.
The following specific objectives will be pursued:

  1. To assess the protective role of recombinant proteins (Sap2 and mannoproteins) as potential candidate vaccine against mucosal candidiasis
  2. Evaluation of protective role of vaginal dendritic cells in mucosal candidiasis .
  3. Isolation and identification of Candida spp. from vaginal fluids taken from women with recurrent vaginitis and carriers.
  4. Detection of cytokine expression in women with recurrent vaginitis and carriers.
  5. Expression of C. albicans proteinase genes in the oral and vaginal fluids by RT-PCR and Real time PCR.
Evaluation of pathogenicity of Candida isolates in animal models .

Achievements of the Working Group in last year (250 words)

The host response against vaginal candidiasis has been investigated in a mouse model of vaginal infection.
Our studies evidenced the elicitation of CMIs and Ab mediated immunity with a Th1 protective immunity. To further investigate the host defense mechanisms at vaginal level we have evaluated the role of the Toll like receptors (TLRs) and C-type lectin like receptors (CLRs) that positively or negatively modulate innate and adoptive immunity in vaginal candidiasis. The role of TLR in protection against vaginal infection was evaluated in mice with different TLR knocked out genes. These results suggest that TLRs and CLRs have a role in the innate and adaptive immunity to Candida at vaginal level. In particular, the findings that TLR4 and Dectin 1 are both required for the induction of acquired protective immunity to the fungus is of interest. Then, we investigated the relationship between recurrent vulvovaginal candidiasis (RVVC) and immune mediators in vaginal fluids of women. Preliminary results indicate that women with RVVC had elevated concentration of IL-4, IL-5 and IL-13 in vaginal fluids.
Women with RVVC may have acquired a local immune defect which can influence the induction of cytokine production and may induce suppression of Th-1 immune response. The immune suppression may be the cause of their symptoms and Candida proliferation. Although C.parapsilosis is frequenlyt isolated from human vaginal infections and it is a complex of different species, the pathogenic potential of C. parapsilosis, C. metapsilosis and C. orthopsilosis was also compared in an in vivo model of murine vaginal candidiasis. The results obtained indicate that C. orthopsilosis and C. metapsilosis are able to induce overt vaginitis in oestrogen-treated mice in a similar way to C. parapsilosis and evidenced the reduced pathogenicity of C. metapsilosis in terms of adhesive ability and pathogenic potential, when compared to the other two members of the psilosis group.

Publications and Conference talks

De Bernardis F., Amacker M., Arancia S., Sandini S., Gremion C., Zurbriggen R., Moser C., Cassone A. 2012. A virosomal vaccine against candidal vaginitis: Immunogenicity, efficacy and safety profile in animal models. Vaccine, 30(30), 4490-4498.
Bertini A., De Bernardis F., Hensgens LA., Sandini S., Senesi S., Tavanti A. 2013. Comparison of Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis adhesive properties and pathogenicity. International Journal of  Medical Microbiology 303: 98-103.
De Bernardis F. “Positive and negative immunomodulation in vaginal candidiasis”. Gordon Research Conference, Immunology of Fungal Infections. Galveston, Texas, USA.  16-21 January 2011.
De Bernardis F. “Immunity to Candida Vaginitis”. 18th Congress I.S.H.A.M. Berlin, Germany, 11-15 June 2012.
Antonopoulou S. “Candida vaginitis” 18th Congress I.S.H.A.M. Berlin, Germany, 11-15 June 2012.   

 

Is your Working Group going to continue for the next three years?

Yes, we would like to continue for the next two years.