Invasive candidiasis is a life-threatening Candida spp. infection with high global incidence and unacceptability high mortality rates, with 3 out of 5 infected patients estimated to succumb to the disease mainly due to lack of reliable diagnosis and efficient antifungal therapies. C. albicans is the main invasive candidiasis-causing agent worldwide (~62% of cases), however, species with inferior virulence like C. parapsilosis can also induce the disease, but have much lower incidence (~7% of cases). In line with this, we have shown that whilst healthy mice succumb to systemic infection with C. albicans, they survive and can efficiently clear C. parapsilosis in vivo. We compared the innate immune responses triggered by the two Candida spp. in macrophages, in order to identify signalling pathways underlying resistance and susceptibility towards candidiasis with an ultimate focus on the design of novel immunotherapies for its treatment. RNAseq analysis revealed that C. parapsilosis induces a higher innate pro-inflammatory response than C. albicans, with type I Interferon (IFN) signalling pathway being strongly activated in C. parapsilosis-stimulated macrophages, but not with C. albicans. We have found that activation of type I IFN pathway in macrophages results in enhanced C. albicans killing via an unidentified candidacidal mechanism. Furthermore, we have discovered that C. albicans is able to actively inhibit IFN-b and IL-27 production in macrophages via a fungal-derived molecule secreted during yeast-hyphae phenotype transition. According to our preliminary data, we believe that PGE2 is the main driver of this blockade effect. We are currently aiming to elucidate both the candidacidal mechanism of IFN-b and the C. albicans-driven IFN-b/IL-27 blockade mechanism and assess their potential as therapeutic targets for treatment of invasive candidiasis.

Invasive candidiasis is a life-threatening _Candida_ spp. infection with high global incidence and unacceptability high mortality rates, with 3 out of 5 infected patients estimated to succumb to the disease mainly due to lack of reliable diagnosis and efficient antifungal therapies. _C. albicans_ is the main invasive candidiasis-causing agent worldwide (~62% of cases), however, species with inferior virulence like _C. parapsilosis_ can also induce the disease, but have much lower incidence (~7% of cases). In line with this, we have shown that whilst healthy mice succumb to systemic infection with _C. albicans_, they survive and can efficiently clear _C. parapsilosis in vivo_. We compared the innate immune responses triggered by the two _Candida_ spp. in macrophages, in order to identify signalling pathways underlying resistance and susceptibility towards candidiasis with an ultimate focus on the design of novel immunotherapies for its treatment. RNAseq analysis revealed that _C. parapsilosis_ induces a higher innate pro-inflammatory response than _C. albicans_, with type I Interferon (IFN) signalling pathway being strongly activated in _C. parapsilosis_-stimulated macrophages, but not with _C. albicans_. We have found that activation of type I IFN pathway in macrophages results in enhanced _C. albicans_ killing via an unidentified candidacidal mechanism. Furthermore, we have discovered that _C. albicans_ is able to actively inhibit IFN-b and IL-27 production in macrophages via a fungal-derived molecule secreted during yeast-hyphae phenotype transition. According to our preliminary data, we believe that PGE2 is the main driver of this blockade effect. We are currently aiming to elucidate both the candidacidal mechanism of IFN-b and the _C. albicans_-driven IFN-b/IL-27 blockade mechanism and assess their potential as therapeutic targets for treatment of invasive candidiasis.

C. albicans VS C. parapsilosis: Exploring differences in the macrophage immune response induced by two distant cousins

Exploring the intricacies of host-pathogen communication is vital in order to understand why
some microbes persist within a host, while others are effectively cleared. As such,
host-pathogen communication is an urgent area of research underpinning human health
and disease, especially given the emerging concerns of antibiotic resistance.
Understanding host-pathogen pathways requires intricate knowledge in the fields of both
microbiology and immunology.

Living in a world of specialists, where scientists sometimes invest their whole career
studying one organism, a specific pathway or a protein, multidisciplinary discussions of
host-pathogen interactions are highly needed. This international conference will provide
such a forum for scientific exchange at the highest level, between scientists from different
research areas related to host-pathogen interactions, with the aim to trigger fruitful
collaborations addressing the urgent questions in the field.

This meeting has an additional special focus of bringing researchers from Ireland, Denmark
and Israel together to learn about cutting edge biology and form new collaborations.
Thus, the conference will be a showcase for the exciting and original research emanating
from these three small but innovative countries.