Staphylococcal manipulation of host immune responses

Abstract

Staphylococcus aureus evades innate and adaptive immune responses to cause localized or systemic infections in humans. Because the development of protective immunity is prevented, S. aureus infections reoccur even with antibiotic or surgical therapy. Mechanisms have been revealed whereby products secreted by S. aureus interfere with neutrophil chemotaxis, complement activation, opsonization and phagocytic killing of bacteria. Immune evasion determinants can interact with host factors from humans, but not with counterparts from other vertebrates, which presents a challenge for the development of animal models. The hallmark of S. aureus is the secretion of coagulases that associate with prothrombin to generate fibrin clots. Through the fibrinogen and fibrin binding attributes of staphylococcal surface proteins, the pathogen shields itself from host phagocytes, which is a prerequisite for abscess lesion formation in infected tissues. Macrophage access to these lesions is restricted by staphylococcal-induced degradation of neutrophil extracellular traps (NETs). Staphylococcal protein A (SpA) crosslinks B cell receptors and triggers proliferative expansion of V_H3⁺ B cells and the secretion of antibodies that fail to recognize S. aureus antigens. SpA blocks host antibody responses that are required for the establishment of protective immunity. T cell superantigens crosslink major histocompatibility class II molecules of antigen-presenting cells with the T cell receptor, promoting lymphocyte proliferation, anergy and the release of cytokines (a cytokine storm). Superantigens vary between S. aureus strains and activate distinct subsets of Vβ chain T cell receptors, endowing staphylococcal isolates with unique T cell-avoidance attributes. Genome sequencing of S. aureus isolates from humans or domesticated animals revealed that only some immune evasion genes are conserved among all strains. Even conserved genes display sequence polymorphisms, which presents a formidable challenge for the design of S. aureus vaccines. Panoplies of immune evasion factors endow staphylococcal strains with unique virulence attributes and with the ability for epidemic spread.