Dissecting the Human Response to Staphylococcus aureus Systemic Infections

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.

Host-induced cell wall remodelling impairs opsonophagocytosis ofStaphylococcus aureusby neutrophils

“…Neutrophils are a key host defence against S. aureus infection and are recruited to the site of infection from the bloodstream [6,7,8,9,10,11]. The detection of S. aureus by neutrophils is largely dependent upon opsonisation of bacteria by bound antibody and complement, which is enabled in most people by the presence of antibodies against a range of different staphylococcal surface proteins [10,11,12,13]. The binding of neutrophils to opsonins on the surface of S. aureus occurs via dedicated receptors and triggers phagocytosis of the pathogen followed by the subsequent exposure of ingested bacteria to a raft of bactericidal products including reactive oxygen species, antimicrobial peptides and proteases [11,12].…”

“…To combat the threat posed by neutrophils, S. aureus has evolved numerous mechanisms of evading opsoninic complement and antibody [12,13,14,15]. For example, S. aureus produces two immunoglobulin binding proteins, Spa and Sbi, that reduce antibody-mediated opsonisation, whilst the production of proteins such as SCIN, Efb and CHIPS reduces complement deposition, activation and detection by immune cells [12][13][14][15][16][17][18][19][20][21][22][23][24]. As such, the bacterial cell surface is a critically important determinant in immune detection of S. aureus and efforts by the pathogen to evade surveillance and killing by host defences.…”

“…Neutrophils are a key host defence against S. aureus infection and are recruited to the site of infection from the bloodstream [6,7,8,9,10,11]. The detection of S. aureus by neutrophils is largely dependent upon opsonisation of bacteria by bound antibody and complement, which is enabled in most people by the presence of antibodies against a range of different staphylococcal surface structures, including wall and lipoteichoic acids (WTA, LTA), peptidoglycan, capsular polysaccharide and proteins [10,11,12,13,14,15,16,17,18]. Whilst the precise abundance of antibody against each of the major surface structures varies from person to person, antibody against each macromolecule has been demonstrated to be sufficient to trigger opsonophagocytosis [14,15,16,17,18,19,20].…”

“…The binding of neutrophils to opsonins on the surface of S. aureus occurs via dedicated receptors and triggers phagocytosis of the pathogen followed by the subsequent exposure of ingested bacteria to a raft of bactericidal products including reactive oxygen species, antimicrobial peptides and proteases [11,12].…”

“…To combat the threat posed by neutrophils, S. aureus has evolved numerous mechanisms of evading opsonic complement and antibody [12,13,21,22]. For example, S. aureus produces two immunoglobulin binding proteins, Spa and Sbi, that reduce antibody-mediated opsonisation, whilst the production of proteins such as SCIN, Efb and CHIPS reduces complement deposition and activation and detection by immune cells [12,13,21,22,23,24,25,26,27,28,29,30,31].…”