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Differential Recognition of Clinically Relevant Sporothrix Species by Human Granulocytes
Ana K Galván-Hernández1, Manuela Gómez-Gaviria1, Iván Martínez-Duncker2
1Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Noria Alta s/n, col. Noria Alta, C.P., Guanajuato Gto. 36050, Mexico.
Abstract:
Sporotrichosis is a cutaneous mycosis that affects humans and animals and has a worldwide distribution. This infection is mainly caused by Sporothrix schenckii, Sporothrix brasiliensis, and Sporothrix globosa. Current research about anti-Sporothrix immunity has been mainly focused on S. schenckii and S. brasiliensis, using different types of human or animal immune cells. Granulocytes are a group of cells relevant for cytokine production, with the capacity for phagocytosis and the generation of neutrophil extracellular traps (NETs). Considering their importance, this study aimed to compare the capacity of human granulocytes to stimulate cytokines, uptake, and form NETs when interacting with different Sporothrix species. We found that conidia, germlings, and yeast-like cells from S. schenckii, S. brasiliensis, and S. globosa play an important role in the interaction with these immune cells, establishing morphology- and species-specific cytokine profiles. S. brasil-iensis tended to stimulate an anti-inflammatory cytokine profile, whilst the other two species had a proinflammatory one. S. globosa cells were the most phagocytosed cells, which occurred through a dectin-1-dependent mechanism, while the uptake of S. brasiliensis mainly occurred via TLR4 and CR3. Cell wall N-linked and O-linked glycans, along with β-1,3-glucan, played a significant role in the interaction of these Sporothrix species with human granulocytes. Finally, this study indicates that conidia and yeast-like cells are capable of inducing NETs, with the latter being a better stimulant. To the best of our knowledge, this is the first study that reports the cytokine profiles produced by human granulocytes interacting with Sporothrix cells.
Insights
Human granulocytes interact differently with Sporothrix species, influencing immune responses and neutrophil extracellular trap (NET) formation. This study reveals species-specific cytokine profiles and recognition mechanisms in sporotrichosis immunity.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Sporotrichosis is a fungal infection caused by Sporothrix species, primarily affecting the skin.
- Immune responses to Sporothrix, particularly Sporothrix schenckii and Sporothrix brasiliensis, are crucial for controlling infection.
- Granulocytes play a key role in innate immunity through cytokine production, phagocytosis, and neutrophil extracellular trap (NET) formation.
Purpose of the Study:
- To compare the capacity of human granulocytes to stimulate cytokines, uptake, and form NETs when interacting with different Sporothrix species (S. schenckii, S. brasiliensis, and S. globosa).
- To elucidate species-specific and morphology-dependent immune interactions in sporotrichosis.
Main Methods:
- Human granulocytes were co-cultured with conidia, germlings, and yeast-like cells of S. schenckii, S. brasiliensis, and S. globosa.
- Cytokine production, phagocytosis, and NET formation were analyzed.
- Mechanisms of interaction, including dectin-1, TLR4, and CR3 involvement, were investigated.
- The role of cell wall components like N-linked and O-linked glycans and β-1,3-glucan was assessed.
Main Results:
- Human granulocytes exhibited species-specific cytokine profiles upon interaction with Sporothrix species.
- S. brasiliensis induced an anti-inflammatory cytokine profile, while S. schenckii and S. globosa induced a proinflammatory profile.
- S. globosa cells were most effectively phagocytosed via dectin-1, whereas S. brasiliensis uptake involved TLR4 and CR3.
- Both conidia and yeast-like cells induced NETs, with yeast-like cells being more potent stimulants.
- Cell wall glycans and β-1,3-glucan significantly influenced granulocyte interactions.
Conclusions:
- Human granulocytes mount distinct immune responses to different Sporothrix species, impacting sporotrichosis pathogenesis.
- The study provides novel insights into the differential recognition mechanisms and immune cell activation by various Sporothrix species.
- Understanding these interactions is vital for developing targeted therapies against sporotrichosis.
