Phagocyte subsets and lymphocyte clonal deletion behind ineffective immune response to Staphylococcus aureus.

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 Rev

authors

Pozzi C,Lofano G,Mancini F,Soldaini E,Speziale P,De Gregorio E,Rappuoli R,Bertholet S,Grandi G,Bagnoli F

doi

10.1093/femsre/fuv024

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

750-63

issue

5

eissn

0168-6445

issn

1574-6976

pii

fuv024

journal_volume

39

pub_type

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