54:
Basophils and IL-4 Dampen the Protective Innate Immune Response Against Cutaneous Staphylococcus aureus Infection.
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Raif S. Geha, MD FAAAAI, Juan-Manuel Leyva-Castillo, PhD
RATIONALE: Staphylococcus aureus (S. aureus) is responsible for the majority of bacterial skin and soft tissue infections. Furthermore, S. aureus is commonly present in patients with atopic dermatitis, a disease characterized by scratching, which inflicts mechanical injury to the skin. It is currently not fully understood how S. aureus evades the protective immune response mounted by the host. We investigated the regulation of skin innate immune response to S. aureus infection of mechanically injured skin.

METHODS: Mechanical injury was induced by tape stripping in wild-type, Il17a-/-, Il4-/- and diphtheria toxin-injected Mcpt8DTR basophil deficient mice. S. aureus was superficially applied on tape stripped skin. mRNA levels and cell infiltrates in treated skin were analyzed by RT-qPCR and flow cytometry respectively. Bacterial burden was evaluated by counting colony-forming units in skin homogenates.

RESULTS: Mechanical skin injury promoted Il17a expression that increased further following S. aureus infection. IL-17A was required for neutrophil recruitment, antimicrobial peptides (AMPs) production and clearance of S. aureus. Mechanical skin injury caused basophil infiltration and Il4 mRNA upregulation in the skin. These changes were accentuated by superimposed S. aureus infection. Il17a mRNA levels, neutrophil infiltration and AMP expression were all increased in tape stripped skin of IL-4 and basophil-deficient mice, and increased further following S. aureus infection. Importantly, these mice showed enhanced S. aureus clearance.

CONCLUSIONS: These findings demonstrate that basophils and IL-4 suppress the IL-17A-mediated protective response against superficial cutaneous S. aureus infection, suggesting that blockade of basophils and/or IL-4 may be beneficial against S. aureus skin infections.