Abstract
Numerous human diseases can be associated with fungal infections either as potential causative agents or as a result of changed immune status due to a primary disease. Fungal infections caused by Candida species can vary from mild to severe dependent upon the site of infection, length of exposure, and past medical history. Patients with impaired immune status are at increased risk for chronic fungal infections. Recent epidemiologic studies have revealed the increasing incidence of candidiasis caused by non-albicans species such as Candida parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response toward this species. In the first section of our study we compared the interaction of CLIB 214 and GA1 cells with murine and human macrophages. Both strains are commonly used to investigate C. parapsilosis virulence properties. CLIB 214 is a rapidly pseudohyphae-forming strain and GA1 is an isolate that mainly exists in a yeast form. Our results showed, that the phagocyte response was similar in terms of overall uptake, however differences were observed in macrophage migration and engulfment of fungal cells. As C. parapsilosis releases extracellular lipases in order to promote host invasion we further investigated the role of these secreted components during the distinct stages of the phagocytic process. Using a secreted lipase deficient mutant strain and the parental strain GA1 individually and simultaneously, we confirmed that fungal secreted lipases influence the fungi's virulence by detecting altered innate cellular responses. In this study we report that two isolates of a single species can trigger markedly distinct host responses and that lipase secretion plays a role on the cellular level of host–pathogen interactions.
Highlights
Candida species are the most common etiological agents of systemic fungal infections (Gácser et al, 2005)
We compared the phagocytic kinetics of three Candida species, C. albicans, C. glabrata, and C. parapsilosis CLIB 214 (Tóth et al, 2014b)
In order to study the interaction between the innate immune system and C. parapsilosis clinical isolates on the cellular level, live cell imaging was used, which has previously been validated as a high-throughput image analysis tool for quantitative analysis (Bain et al, 2014; Okai et al, 2015)
Summary
Candida species are the most common etiological agents of systemic fungal infections (Gácser et al, 2005). Candida albicans is the leading Candida species responsible for bloodstream infections, a significant increase has been reported in the number of fungal invasions caused by nonalbicans Candida (NAC) species (Guinea, 2014). GA1 and CLIB 214 are two distinct C. parapsilosis clinical isolates that are the most frequently used model strains for biological and molecular characterization studies (Gácser et al, 2005; Holland et al, 2014). C. parapsilosis GA1 is a bloodstream isolate obtained in Hamburg, Germany, and primarily appears in a yeast form and produces smooth colonies on agar (Trofa et al, 2008; Pryszcz et al, 2013). C. parapsilosis CLIB 214 (ATCC 22019) was isolated from the feces of a patient in Puerto Rico, and rapidly forms pseudohyphae producing a rough, concentric colony phenotype on agar (Laffey and Butler, 2005; Nosek et al, 2009). No comparison has been made between the virulence of these commonly used laboratory type strains
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