While C. albicans remains the most clinically significant Candida species, C. parapsilosis is an emerging pathogen with increased affinity to neonates. Syk/CARD9 signaling is crucial in immunity to C. albicans , but its role in in vivo responses to other pathogenic Candida species is largely unexplored.

Mannans are components of the fungal wall attached to proteins via N- or O-linkages. In Candida albicans, Och1 is an α1,6-mannosyltransferase that adds the first mannose unit to the N-linked mannan outer chain; whereas Pmr1 is an ion pump that imports Mn2+ into the Golgi lumen. This cation is the cofactor of Golgi-resident mannosyltransferases, and thus Pmr1 is involved in the synthesis of both N- and O-linked mannans. Since we currently have limited information about the genetic network behind the Candida tropicalis protein mannosylation machinery, we disrupted OCH1 and PMR1 in this organism. The C. tropicalis pmr1Δ and och1Δ mutants showed increased doubling times, aberrant colony and cellular morphology, reduction in the wall mannan content, and increased susceptibility to wall perturbing agents. These changes were accompanied by increased exposure of both β1,3-glucan and chitin at the wall surface of both mutant strains. Our results showed that O-linked mannans are dispensable for cytokine production by human mononuclear cells, but N-linked mannans and β1,3-glucan are key ligands to trigger cytokine production in a co-stimulatory pathway involving dectin-1 and mannose receptor. Moreover, we found that the N-linked mannan core found on the surface of C. tropicalis och1Δ null mutant was capable of inducing cytokine production; and that a mannan-independent pathway for IL-10 production is present in the C. tropicalis-mononuclear cell interaction. Both mutant strains showed virulence attenuation in the Galleria mellonella and the mouse model of systemic candidiasis. Therefore, mannans are relevant for cell wall composition and organization, and for the C. tropicalis-host interaction.

Our skin provides immunological protection against several pathogens. Skin epithelial cells respond to microbial stimuli in various ways, such as through the production of antimicrobial peptides or secretion of cytokines, although phagocytosis of potentially evading microbes was also reported. Relatively little is known about how skin keratinocytes differentiate between the presence of pathogenic and commensal fungi. In this project, we aimed to investigate how human keratinocytes interact with different Candida species, as common colonizers of the skin. While C. albicans is a common cause of cutaneous candidiasis, C. parapsilosisis rarely associated with this disease.For the experimentshuman skin keratinocyte cell lines (HaCaT, HPV-KER)were applied andchallengedwith C. albicans (SC5314 and WO1 strains) and C. parapsilosis (GA1 and CLIB214 strains)strains.We aimedto determine the extent to which C. albicans and C. parapsilosis damage human keratinocytes, their attachment to host cells, the keratinocytes’ ability to internalize these fungi and to examinecytokine production in response to stimuli. Our results suggest that C. albicans causes significantly more damage to human keratinocytes than C. parapsilosis and the HPV-KER cell line was more susceptibleto the infection. In both HaCaT and HPV-KER cells, the production of IL-6, IL-8, and CCL5 increased primarilyafter C. albicans infection. Based on the adhesion studies, there was a low degree of association in case of C. parapsilosis GA1 and CLIB214 compared to C. albicans SC5314 and WO1.