Staphylococcus aureus Colonization: Modulation of Host Immune Response and Impact on Human Vaccine Design

Abstract

In apparent contrast to its invasive potential Staphylococcus aureus colonizes the anterior nares of 20-80% of the human population. The relationship between host and microbe appears particularly individualized and colonization status seems somehow predetermined. After decolonization, persistent carriers often become re-colonized with their prior S. aureus strain, whereas non-carriers resist experimental colonization. Efforts to identify factors facilitating colonization have thus far largely focused on the microorganism rather than on the human host. The host responds to S. aureus nasal colonization via local expression of anti-microbial peptides, lipids, and cytokines. Interplay with the co-existing microbiota also influences colonization and immune regulation. Transient or persistent S. aureus colonization induces specific systemic immune responses. Humoral responses are the most studied of these and little is known of cellular responses induced by colonization. Intriguingly, colonized patients who develop bacteremia may have a lower S. aureus-attributable mortality than their non-colonized counterparts. This could imply a staphylococcal-specific immune "priming" or immunomodulation occurring as a consequence of colonization and impacting on the outcome of infection. This has yet to be fully explored. An effective vaccine remains elusive. Anti-S. aureus vaccine strategies may need to drive both humoral and cellular immune responses to confer efficient protection. Understanding the influence of colonization on adaptive response is essential to intelligent vaccine design, and may determine the efficacy of vaccine-mediated immunity. Clinical trials should consider colonization status and the resulting impact of this on individual patient responses. We urgently need an increased appreciation of colonization and its modulation of host immunity.

Keywords: Staphylococcus aureus; T cells; colonization; host response; immunomodulation; microbiota; vaccine.

Figure 1

Staphylococcus aureus factors facilitating colonization. Bacterial strategies and attributes known to facilitate colonization by mediating adhesion to the nasal epithelium or by actively evading host mechanisms of bacterial clearance. Those established in colonization settings and in vivo have been included, although several other immune-evasion mechanisms have been described in infection models or in vitro. ClfB, clumping factor B; IsdA, iron-regulated surface determinant A; MrpF, multiple resistance and pH regulation protein F.

Figure 2

Proposed immunomodulation affecting and resulting from colonization in persistent and non-persistent carriage. (A) The epithelium and local environment of the nares in individuals with S. aureus carriage may be more favorable for colonization with high levels of host ligands to facilitate adhesion, and reduced concentrations of the potent anti-staphylococcal peptide human β-defensin 3 (hBD-3) in nasal secretions. Interaction and processing of S. aureus by local antigen-presenting cells may result in an immune tolerance and suppression of pro-inflammatory responses. Inhibition of bacterial clearance would allow persistent colonization. (B) In non-carriers, the local environment and response might resist successful S. aureus colonization. Nasal secretions may contain higher levels of hBD-3 or other anti-microbial peptides. Local immune response to the organism could be more pro-inflammatory and promote the expansion of Th17 cells to attract neutrophils and create local inflammation that facilitates bacterial clearance.

Figure 3

Outline model of a protective vaccine against S. aureus infection. A vaccine may be universal or specifically target high-risk groups. It should ideally aim to elicit humoral, cellular, and phagocytic responses.