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Published on: July 16, 2019
Staphylococcal γ-hemolysins induce IL-4 production in murine basophils
Ayana Ogata1, Kazuhito Hayashi1, Takuma Kitano1
1Department of Molecular and Cellular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya, 467-8603, Japan.
Abstract:
Basophils are known to produce a large amount of IL-4 in response to stimuli and play a role in the initiation and propagation of type 2 inflammations. S. aureus secretes a series of pore-forming toxins: α-hemolysin, γ-hemolysins, and leukocidins. In this study, we examined the effects of α-hemolysin, γ-hemolysins (HlgAB and HlgCB), and leukocidins (LukAB, LukED, and Panton-Valentine leukocidin) on the function of basophils. All pore-forming toxins except for Panton-Valentine leukocidin bound to murine bone marrow-derived basophils (BMBs). HlgAB and LukED but not other toxins evoked the leakage of lactate dehydrogenase from BMBs at the concentration of 30 μg/ml γ-hemolysins, HlgAB and HlgCB, induced the secretion of IL-4 in BMBs at concentrations above 3.3 μg/ml. LukAB did not induce, and Hla and LukED induced only a small amount of IL-4. HlgBΔstem, the 5 amino acids deletion mutant of HlgB in the stem region, diminished IL-4 secretion by HlgAB and HlgCB in BMBs. These results suggest that the cell damage and the induction of IL-4 in basophils by HlgAB require pore formation. The induction of IL-4 by γ-hemolysins was also observed in fleshly isolated murine basophils. These results demonstrate a novel function of γ-hemolysins, the induction of IL-4 in basophils, in an IgE-independent manner.
Insights
Staphylococcus aureus pore-forming toxins, specifically gamma-hemolysins, induce Interleukin-4 (IL-4) secretion from basophils. This occurs independently of IgE and requires pore formation, revealing a new role for these toxins in type 2 inflammation.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Basophils are key producers of Interleukin-4 (IL-4), driving type 2 inflammatory responses.
- Staphylococcus aureus secretes various pore-forming toxins, including alpha-hemolysin, gamma-hemolysins, and leukocidins, which can impact immune cells.
Purpose of the Study:
- To investigate the effects of S. aureus pore-forming toxins on basophil function.
- To determine if these toxins can induce IL-4 secretion from basophils and elucidate the mechanisms involved.
Main Methods:
- Murine bone marrow-derived basophils (BMBs) were exposed to purified S. aureus pore-forming toxins.
- Toxin binding, cell membrane integrity (lactate dehydrogenase leakage), and IL-4 secretion were measured.
- Experiments utilized wild-type toxins and a specific mutant (HlgBΔstem) to assess the role of pore formation.
Main Results:
- Most tested toxins bound to BMBs, with HlgAB and LukED causing cell membrane damage.
- Gamma-hemolysins (HlgAB and HlgCB) significantly induced IL-4 secretion from BMBs at concentrations above 3.3 μg/ml.
- IL-4 induction by gamma-hemolysins was dependent on pore formation, as shown by experiments with the HlgBΔstem mutant.
Conclusions:
- S. aureus gamma-hemolysins possess a novel function: inducing IL-4 secretion from basophils in an IgE-independent manner.
- The induction of IL-4 by HlgAB requires pore formation, linking toxin-induced cell damage to immune signaling.
- These findings highlight a new mechanism by which S. aureus toxins can contribute to type 2 inflammation.
