Abstract:
:Lack of known mechanisms of protection against Staphylococcus aureus in humans is hindering development of efficacious vaccines. Preclinical as well as clinical data suggest that antibodies play an important role against S. aureus. For instance, certain hypogammaglobulinaemic patients are at increased risk of staphylococcal infections. However, development of effective humoral response may be dampened by converging immune-evasion mechanisms of S. aureus. We hypothesize that B-cell proliferation induced by staphylococcal protein A (SpA) and continuous antigen exposure, without the proper T-cell help and cytokine stimuli, leads to antigen-activated B-cell deletion and anergy. Recent findings suggest an important role of type I neutrophils (PMN-I) and conventionally activated macrophages (M1) against S. aureus, while alternatively activated macrophages (M2) favour biofilm persistence and sepsis. In addition, neutrophil-macrophage cooperation promotes extravasation and activation of neutrophils as well as clearance of bacteria ensnared in neutrophil extracellular traps. Activation of these processes is modulated by cytokines and T cells. Indeed, low CD4(+) T-cell counts represent an important risk factor for skin infections and bacteraemia in patients. Altogether, these observations could lead to the identification of predictive correlates of protection and ways for shifting the balance of the response to the benefit of the host through vaccination.
journal_name
FEMS Microbiol Revjournal_title
FEMS microbiology reviewsauthors
Pozzi C,Lofano G,Mancini F,Soldaini E,Speziale P,De Gregorio E,Rappuoli R,Bertholet S,Grandi G,Bagnoli Fdoi
10.1093/femsre/fuv024subject
Has Abstractpub_date
2015-09-01 00:00:00pages
750-63issue
5eissn
0168-6445issn
1574-6976pii
fuv024journal_volume
39pub_type
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