Limits...
Opportunistic pathogen Candida albicans elicits a temporal response in primary human mast cells.

Lopes JP, Stylianou M, Nilsson G, Urban CF - Sci Rep (2015)

Bottom Line: Initially mast cells reduced fungal viability and occasionally internalized yeasts.C. albicans-infected mast cells formed extracellular DNA traps, which ensnared but did not kill the fungus.Our results suggest that mast cells serve as tissue sentinels modulating antifungal immune responses during C. albicans infection.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Clinical Microbiology, Umeå University, Umeå, Sweden [2] Umeå Centre for Microbial Research (UCMR), Umeå, Sweden [3] The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå, Sweden.

ABSTRACT
Immunosuppressed patients are frequently afflicted with severe mycoses caused by opportunistic fungal pathogens. Besides being a commensal, colonizing predominantly skin and mucosal surfaces, Candida albicans is the most common human fungal pathogen. Mast cells are present in tissues prone to fungal colonization being expectedly among the first immune cells to get into contact with C. albicans. However, mast cell-fungus interaction remains a neglected area of study. Here we show that human mast cells mounted specific responses towards C. albicans. Collectively, mast cell responses included the launch of initial, intermediate and late phase components determined by the secretion of granular proteins and cytokines. Initially mast cells reduced fungal viability and occasionally internalized yeasts. C. albicans could evade ingestion by intracellular growth leading to cellular death. Furthermore, secreted factors in the supernatants of infected cells recruited neutrophils, but not monocytes. Late stages were marked by the release of cytokines that are known to be anti-inflammatory suggesting a modulation of initial responses. C. albicans-infected mast cells formed extracellular DNA traps, which ensnared but did not kill the fungus. Our results suggest that mast cells serve as tissue sentinels modulating antifungal immune responses during C. albicans infection. Consequently, these findings open new doors for understanding fungal pathogenicity.

No MeSH data available.


Related in: MedlinePlus

Neutrophils but not monocytes differentially migrated in response to supernatants from mast cells infected with C. albicans.Supernatants collected from C. albicans-infected mast cells (MOI 0.1) at 6 h, 12 h and overnight infection were used as chemoattractants to neutrophils and monocytes in a transwell system. End-point cell migration was plotted per condition, per time as ratio of migrated cells using as 100% control cells added to the lower compartment without inserted transwell system. (A) Neutrophil migration is increased over time towards supernatants of infection but not to C. albicans and HMC-1 alone (controls). (B) Monocytes show no significant chemoattraction towards supernatants of infected mast cells. Variations between neutrophil or monocyte migration over time towards supernatants of infection and C. albicans control were analysed for statistical significance using a one-way ANOVA with Tukey post-test. As positive control for migration we used fMLP causing chemotaxis significantly above background of approximately 45% after 30 min for neutrophils and 13% after 90 min for monocytes. These values are indicated as a horizontal, dashed line in the graphs of the figure. Data are presented as means of n = 5 (3) ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4507480&req=5

f2: Neutrophils but not monocytes differentially migrated in response to supernatants from mast cells infected with C. albicans.Supernatants collected from C. albicans-infected mast cells (MOI 0.1) at 6 h, 12 h and overnight infection were used as chemoattractants to neutrophils and monocytes in a transwell system. End-point cell migration was plotted per condition, per time as ratio of migrated cells using as 100% control cells added to the lower compartment without inserted transwell system. (A) Neutrophil migration is increased over time towards supernatants of infection but not to C. albicans and HMC-1 alone (controls). (B) Monocytes show no significant chemoattraction towards supernatants of infected mast cells. Variations between neutrophil or monocyte migration over time towards supernatants of infection and C. albicans control were analysed for statistical significance using a one-way ANOVA with Tukey post-test. As positive control for migration we used fMLP causing chemotaxis significantly above background of approximately 45% after 30 min for neutrophils and 13% after 90 min for monocytes. These values are indicated as a horizontal, dashed line in the graphs of the figure. Data are presented as means of n = 5 (3) ± SD.

Mentions: As some of the chemokines from our multiplex screening are relevant in host immune cell recruitment, we next tested the chemoattractive potential of supernatants from C. albicans-infected mast cells towards neutrophils and monocytes. Mast cells were infected for three time points and supernatants harvested. The chemotactic potential of the supernatants was tested using fluorescently labelled neutrophils in a transwell system (Fig. 2A). Chemoattractant fMLF was used as positive control32.


Opportunistic pathogen Candida albicans elicits a temporal response in primary human mast cells.

Lopes JP, Stylianou M, Nilsson G, Urban CF - Sci Rep (2015)

Neutrophils but not monocytes differentially migrated in response to supernatants from mast cells infected with C. albicans.Supernatants collected from C. albicans-infected mast cells (MOI 0.1) at 6 h, 12 h and overnight infection were used as chemoattractants to neutrophils and monocytes in a transwell system. End-point cell migration was plotted per condition, per time as ratio of migrated cells using as 100% control cells added to the lower compartment without inserted transwell system. (A) Neutrophil migration is increased over time towards supernatants of infection but not to C. albicans and HMC-1 alone (controls). (B) Monocytes show no significant chemoattraction towards supernatants of infected mast cells. Variations between neutrophil or monocyte migration over time towards supernatants of infection and C. albicans control were analysed for statistical significance using a one-way ANOVA with Tukey post-test. As positive control for migration we used fMLP causing chemotaxis significantly above background of approximately 45% after 30 min for neutrophils and 13% after 90 min for monocytes. These values are indicated as a horizontal, dashed line in the graphs of the figure. Data are presented as means of n = 5 (3) ± SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4507480&req=5

f2: Neutrophils but not monocytes differentially migrated in response to supernatants from mast cells infected with C. albicans.Supernatants collected from C. albicans-infected mast cells (MOI 0.1) at 6 h, 12 h and overnight infection were used as chemoattractants to neutrophils and monocytes in a transwell system. End-point cell migration was plotted per condition, per time as ratio of migrated cells using as 100% control cells added to the lower compartment without inserted transwell system. (A) Neutrophil migration is increased over time towards supernatants of infection but not to C. albicans and HMC-1 alone (controls). (B) Monocytes show no significant chemoattraction towards supernatants of infected mast cells. Variations between neutrophil or monocyte migration over time towards supernatants of infection and C. albicans control were analysed for statistical significance using a one-way ANOVA with Tukey post-test. As positive control for migration we used fMLP causing chemotaxis significantly above background of approximately 45% after 30 min for neutrophils and 13% after 90 min for monocytes. These values are indicated as a horizontal, dashed line in the graphs of the figure. Data are presented as means of n = 5 (3) ± SD.
Mentions: As some of the chemokines from our multiplex screening are relevant in host immune cell recruitment, we next tested the chemoattractive potential of supernatants from C. albicans-infected mast cells towards neutrophils and monocytes. Mast cells were infected for three time points and supernatants harvested. The chemotactic potential of the supernatants was tested using fluorescently labelled neutrophils in a transwell system (Fig. 2A). Chemoattractant fMLF was used as positive control32.

Bottom Line: Initially mast cells reduced fungal viability and occasionally internalized yeasts.C. albicans-infected mast cells formed extracellular DNA traps, which ensnared but did not kill the fungus.Our results suggest that mast cells serve as tissue sentinels modulating antifungal immune responses during C. albicans infection.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Clinical Microbiology, Umeå University, Umeå, Sweden [2] Umeå Centre for Microbial Research (UCMR), Umeå, Sweden [3] The Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå, Sweden.

ABSTRACT
Immunosuppressed patients are frequently afflicted with severe mycoses caused by opportunistic fungal pathogens. Besides being a commensal, colonizing predominantly skin and mucosal surfaces, Candida albicans is the most common human fungal pathogen. Mast cells are present in tissues prone to fungal colonization being expectedly among the first immune cells to get into contact with C. albicans. However, mast cell-fungus interaction remains a neglected area of study. Here we show that human mast cells mounted specific responses towards C. albicans. Collectively, mast cell responses included the launch of initial, intermediate and late phase components determined by the secretion of granular proteins and cytokines. Initially mast cells reduced fungal viability and occasionally internalized yeasts. C. albicans could evade ingestion by intracellular growth leading to cellular death. Furthermore, secreted factors in the supernatants of infected cells recruited neutrophils, but not monocytes. Late stages were marked by the release of cytokines that are known to be anti-inflammatory suggesting a modulation of initial responses. C. albicans-infected mast cells formed extracellular DNA traps, which ensnared but did not kill the fungus. Our results suggest that mast cells serve as tissue sentinels modulating antifungal immune responses during C. albicans infection. Consequently, these findings open new doors for understanding fungal pathogenicity.

No MeSH data available.


Related in: MedlinePlus