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

Abstract

† Aisling F. Brown and John M. Leech have contributed equally to this work.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.

Correlation between Nasal Microbiome Composition and Remote Purulent Skin and Soft Tissue Infections

“…Although vaccine studies have been largely ineffective at preventing S. aureus carriage in humans (17,45,46), a greater understanding of the nature of the apparent competition between S. aureus and other taxa may hold promise for future therapeutic design to prevent S. aureus carriage and SSTI development. Although bacterial antagonism against S. aureus has previously been investigated (41,43,47,48), our data suggest that there are additional variables to consider when prophylactic countermeasures are being designed; in order to lower the risk of development of SSTI, one must lower S. aureus colonization levels but must be cognizant of other nasal bacterial inhabitants, especially from the phylum Proteobacteria.…”

“…While it is clear that host genetics, immune responses, and strain differences contribute (12)(13)(14)(15)(16)(17), there are likely other important factors. As the anterior nares appear to be a critical S. aureus reservoir (1,18,19) and because antecedent nasal carriage increases the risk for infection (1,20,21), a better understanding of nasal microbial ecology may yield valuable clues regarding SSTI susceptibility.…”

New <i>Spa</i> Types among MRSA and MSSA Isolates in North of Iran

“…This bacterium responsible for a variety of disorders ranging from superficial skin infections up to serious abnormalities such as pneumonia, Bacteremia and Endocarditis and Staphylococcus aureus colonizes the anterior nares of 20% -80% of the human population [1] [2].…”

IL-10 Plays Opposing Roles during Staphylococcus aureus Systemic and Localized Infections

“…Staphylococcus aureus is an important component of the normal microbiota of most of the healthy human population (15). However, upon invasive entry it is a potentially lethal opportunistic pathogen and is a leading cause of a variety of communityacquired and hospital-acquired bacterial infections.…”