Modulation of the host immunity

For pathogens breaching mucosal or skin barriers and adhering to host tissues or cells, infection can develop only if other defenses are neutralized, avoided, or restricted. Professional phagocytes such as neutrophils, monocytes, and macrophages provide nonspecific, but powerful, host defenses against pathogens of all types. Neutrophils, in particular, migrate efficiently to sites of infection in response to chemotactic signals, use complement and antibody for pathogen recognition, and kill ingested organisms by oxidative and nonoxidative mechanisms. E. faecalis must overcome the clearance functions of the host system to successfully cause infection. PMNs are a critical component of the human host response against bacterial infections. Invading bacteria may be coated by complement proteins or specific antibodies and subsequently phagocytosed and killed by PMNs. This process of coating of bacteria with complement proteins or antibodies to enhance phagocytosis is called opsonization. Studies involving the role of antibodies and complement in the phagocytic killing of enterococci revealed that PMNs mediated killing depended primarily on complement activation by either the classical or the alternative pathway.

Antibodies to E. faecalis enhanced the PMNs mediated killing, however they were not essential as different studies showed efficient killing also in the presence of serum without gamma globulins . Although antibodies to enterococci are found in humans with enterococcal infections, studies on the efficacy of antibodies to E. faecalis in the prevention of infections are quite contradicting.

Huebner et al. found prophylactic and therapeutic efficacy of antibodies to a capsular polysaccharide in a mouse infective model. In addition, the role of antibodies to the surface protein aggregation substance (Agg) in prevention of endocarditis is underscored by the absence of host antibodies specific for the Agg during the formation of endocardial vegetation. Thereby the bacteria are protected from the influence of the antibodies.

However, another study on the efficacy of antibodies to Agg in the prevention of endocarditis in a rabbit model did not show any protection.  E. faecalis has developed different strategies to overcome the immune response.  

Weeks et al. reported a prolonged intracellular survival of enterococci for up to 72 h in mouse peritoneal macrophages. This property might contribute to the pathogenesis of infections in the way that the enterococci migrate to distant sites in the body and be protected from antimicrobial therapy within the macrophage. In line with these findings are the results of other investigations reporting that Agg promotes direct, opsonin-independent binding of E. faecalis to PMNs and that through this opsonin-independent binding E. faecalis was able to survive inside different phagocytes.

Another study showed that strains expressing gelatinase, cytolysin, or Agg were not more resistant to neutrophil mediated killing, but the in vitro assays were performed under circumstances that might not support expression of these traits or mimic the in vivo situation. The structure of the Esp with multiple repeat motifs in the encoding gene might be important in the immune evasion of infecting E. faecalis.