The Bacterium's New Clothes: Making the Poly-N-Acetyl Glucosamine Surface Polysaccharide Functionally Visible to the Immune System
Poly-N-acetyl glucosamine (PNAG) is a surface polysaccharide expressed by a number of important pathogens. Antibodies induced by the native, highly acetylated form fail to promote opsonic killing and protective immunity, while deacetylated PNAG readily elicits opsonic and protective antibodies. Cerca et al. (p. 3406-3413) show that an N-deacetylase (IcaB) encoded within the PNAG biosynthetic locus of Staphylococcus aureus is needed for producing a PNAG glycoform that can be retained on the bacterial surface. Additionally, overproduction of IcaB increases S. aureus virulence as well as sensitivity to opsonic killing by antibodies that can bind to deacetylated PNAG. These findings provide a likely molecular basis for the superior protective activity of antibody to deacetylated isoforms of PNAG.
The Meningococcal Capsule Is Important for Intracellular Survival
One of the essential attributes for meningococcal pathogenesis is the polysaccharide capsule, which is critical for bacterial survival in extracellular fluids. Spinosa et al. (p. 3594-3603) investigated the role of the meningococcal capsule in intracellular survival in human phagocytic and nonphagocytic cells. They demonstrate that the capsule, which negatively affects bacterial adhesion and entry, is, in contrast, fundamental for intracellular survival of this microorganism. An increased resistance to cationic antimicrobial peptides, key components of the host innate defense system against microbial infections, is a mechanism by which the capsule protects the meningococci in the intracellular environment.
NADPH Oxidase Has a Major Role in the Apoptosis of Phagocytic Neutrophils
The clearance of phagocytic neutrophils from an inflammatory site is crucial for the resolution of inflammation. NADPH oxidase, which generates microbicidal oxidants within the neutrophil phagosome, also appears to have a central role in neutrophil apoptosis. Wilkie et al. (p. 3256-3263) incubated neutrophils with Staphylococcus aureus and showed that those with a functional NADPH oxidase inactivate their apoptotic caspases but trigger phosphatidylserine exposure and uptake by macrophages. This caspase-independent pathway is potentially unique to the neutrophil, with the strong oxidative environment generated during phagocytosis preventing the involvement of the redox-sensitive caspases.
Established CD4 T-Cell Memory Can Be Harnessed To Promote Enhanced Primary CD8 T-Cell Responses against Unrelated Antigens
As implied by their name, CD4 T helper cells facilitate many aspects of CD8 T-cell responses. Using a novel model to examine the role of memory CD4 T cells in vivo, Krawczyk et al. (p. 3556-3560) demonstrate that existing memory Th1, but not Th2, cells can be engaged to promote primary CD8 T-cell responses. These findings raise the possibility that vaccines or immunotherapies aimed at inducing CD8 T-cell responses may benefit from the inclusion of epitopes capable of activating memory CD4 T cells generated by prior infection or immunization.