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Updated: Jul 25, 2025
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
DOCK8 is essential for neutrophil mediated clearance of cutaneous S. aureus infection
Hazel Wilkie1, Maheshwor Timilshina1, Siti Rahmayanti2
1Division of Immunology, Boston Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, MA, USA.
Abstract:
DOCK8 deficient patients are susceptible to skin infection with Staphylococcus aureus which is normally cleared by neutrophils. We examined the mechanism of this susceptibility in mice. Dock8-/- mice had delayed clearance of S. aureus from skin mechanically injured by tape stripping. The numbers and viability of neutrophils in infected but not in uninfected, tape stripped skin were significantly reduced in Dock8-/- mice compared to WT controls. This is despite comparable numbers of circulating neutrophils, and normal to elevated cutaneous expression of Il17a and IL-17A inducible neutrophil attracting chemokines Cxcl1, Cxcl2 and Cxcl3. DOCK8 deficient neutrophils were significantly more susceptible to cell death upon in vitro exposure to S. aureus and exhibited reduced phagocytosis of S. aureus bioparticles but had a normal respiratory burst. Impaired neutrophil survival in infected skin and defective neutrophil phagocytosis likely underlie the susceptibility to cutaneous S. aureus infection in DOCK8 deficiency.
Insights
Deficiency in DOCK8 impairs neutrophil function, leading to delayed Staphylococcus aureus clearance in skin infections. This susceptibility is linked to reduced neutrophil survival and phagocytosis in DOCK8-deficient mice.
Area of Science:
- Immunology
- Dermatology
- Infectious Diseases
Background:
- DOCK8 deficiency is associated with increased susceptibility to bacterial skin infections, particularly Staphylococcus aureus.
- Neutrophils are critical for clearing S. aureus from the skin.
Purpose of the Study:
- To investigate the mechanism underlying increased susceptibility to Staphylococcus aureus skin infections in DOCK8-deficient patients.
- To examine the role of neutrophils in S. aureus clearance in a mouse model of DOCK8 deficiency.
Main Methods:
- Utilized a tape-stripping mouse model to induce skin injury and S. aureus infection.
- Assessed neutrophil numbers, viability, and function (phagocytosis, respiratory burst) in infected skin.
- Analyzed gene expression of neutrophil-attracting chemokines.
Main Results:
- DOCK8-deficient mice exhibited delayed S. aureus clearance from mechanically injured skin.
- Neutrophil numbers and viability were significantly reduced in infected skin of DOCK8-deficient mice compared to controls.
- DOCK8-deficient neutrophils showed increased susceptibility to cell death and reduced phagocytosis of S. aureus in vitro, despite normal respiratory burst.
Conclusions:
- Impaired neutrophil survival and defective phagocytosis in DOCK8 deficiency contribute to susceptibility to cutaneous S. aureus infection.
- These findings highlight a critical role for DOCK8 in neutrophil-mediated host defense against skin pathogens.
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