Abstract
Staphylococcus aureus is a common human commensal and the leading cause of diverse infections. To identify distinctive parameters associated with infection and colonization, we compared the immune and inflammatory responses of patients with a diagnosis of invasive S. aureus disease to healthy donors. We analyzed the inflammatory responses founding a pattern of distinctive cytokines significantly higher in the patients with invasive disease. The measure of antibody levels revealed a wide antibody responsiveness from all subjects to most of the antigens, with significantly higher response for some antigens in the invasive patients compared to control. Moreover, functional antibodies against toxins distinctively associated with the invasive disease. Finally, we examined the genomic variability of isolates, showing no major differences in genetic distribution compared to a panel of representative strains. Overall, our study shows specific signatures of cytokines and functional antibodies in patients with different primary invasive diseases caused by S. aureus. These data provide insight into human responses towards invasive staphylococcal infections and are important for guiding the identification of novel preventive and therapeutic interventions against S. aureus.
Highlights
Staphylococcus aureus is the leading cause of diverse infections that range from uncomplicated skin infections, to more severe diseases, such as pneumonia, sepsis, osteomyelitis, and endocarditis
Capsular polysaccharide genes were characterized showing that strains isolated from patients with invasive disease preferentially encoded capsular polysaccharides type 5 (CP5) locus (35 isolates carrying CP5 and 5 carrying CP8)
We aimed to answer this key question interrogating the hostpathogen interplays by different angles: we performed a genome analysis of bacterial isolates to define the genetic diversity of the causative strains, we analyzed the innate immune response to the infection, and we dissected the adaptive responses through both a whole analysis of antibody repertoire and an antigen-specific examination
Summary
Staphylococcus aureus is the leading cause of diverse infections that range from uncomplicated skin infections, to more severe diseases, such as pneumonia, sepsis, osteomyelitis, and endocarditis. Human Th17 cells and IL-17A/F responses contribute to protective immunity against S. aureus infections, against skin, mucosal, and soft tissue infections, promoting neutrophil and monocyte recruitment from the bloodstream to the site of infection [5]. To protect against tissue damage, a compensatory, anti-inflammatory response is induced by T regulatory cells that downregulate immune responses by producing anti-inflammatory cytokines such as TGFb and IL-10. This balance and timing of the pro- and anti-inflammatory responses induced by S. aureus bacteremia are predictive of clinical outcomes [reviewed in [6]]
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