Innate Immune Memory Contributes to Host Defense against Recurrent Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus

Autor: Norma V. Solis, Lloyd S. Miller, Michael R. Yeaman, Siyang Chaili, Liana C. Chan, Huiyuan Wang, Luis F. Diaz, Colin W. Johnson, Scott G. Filler, Hong K. Lee
Přispěvatelé: Pirofski, Liise-anne
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Gene Expression
Skin infection
medicine.disease_cause
Medical and Health Sciences
Mice
Recurrence
Innate
2.1 Biological and endogenous factors
Aetiology
Mice
Knockout

skin infection
biology
Bacterial Infections
Biological Sciences
Acquired immune system
Infectious Diseases
Staphylococcus aureus
Host-Pathogen Interactions
Cytokines
Staphylococcal Skin Infections
recurrent infection
Disease Susceptibility
Infection
Methicillin-Resistant Staphylococcus aureus
Langerin
Knockout
Immunology
Antimicrobial peptides
Microbiology
Vaccine Related
03 medical and health sciences
Immunity
medicine
Animals
Innate immune system
Agricultural and Veterinary Sciences
Animal
Prevention
Inflammatory and immune system
medicine.disease
immunity
Methicillin-resistant Staphylococcus aureus
Immunity
Innate

Disease Models
Animal

Emerging Infectious Diseases
030104 developmental biology
Disease Models
biology.protein
Parasitology
Immunologic Memory
Spleen
Zdroj: Chan, LC; Chaili, S; Filler, SG; Miller, LS; Solis, NV; Wang, H; et al.(2017). Innate Immune Memory Contributes to Host Defense against Recurrent Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus. INFECTION AND IMMUNITY, 85(2). doi: 10.1128/IAI.00876-16. UCLA: Retrieved from: http://www.escholarship.org/uc/item/7068c7q0
Infection and immunity, vol 85, iss 2
ISSN: 1098-5522
0019-9567
DOI: 10.1128/iai.00876-16
Popis: Staphylococcus aureus is the leading cause of skin and skin structure infections (SSSI). The high frequency of recurring SSSI due to S. aureus , including methicillin-resistant S. aureus (MRSA) strains, despite high titers of specific antibodies and circulating T cells, implies that traditional adaptive immunity imparts incomplete protection. We hypothesized that innate immune memory contributes to the protective host defense against recurring MRSA infection. To test this hypothesis, SSSI was induced in wild-type and rag1 −/− mice in the BALB/c and C57BL/6 backgrounds. Prior infection (priming) of wild-type and rag1 −/− mice of either background afforded protection against repeat infection, as evidenced by reduced abscess severities and decreased CFU densities compared to those in naive controls. Interestingly, protection was greater on the previously infected flank than on the naive flank for wild-type and rag1 −/− mice. For wild-type mice, protective efficacy corresponded to increased infiltration of neutrophils (polymorphonuclear leukocytes [PMN]), macrophages (MΦ), Langerin + dendritic cells (LDC), and natural killer (NK) cells. Protection was associated with the induction of interleukin-17A (IL-17A), IL-22, and gamma interferon (IFN-γ) as well as the antimicrobial peptides CRAMP and mβD-3. Priming also protected rag1 −/− mice against recurring SSSI, with increased MΦ and LDC infiltration and induction of IL-22, CRAMP, and mβD-3. These findings suggest that innate immune memory, mediated by specific cellular and molecular programs, likely contributes to the localized host defense in recurrent MRSA SSSI. These insights support the development of targeted immunotherapeutic strategies to address the challenge of MRSA infection.
Databáze: OpenAIRE