Final Report Summary - B-INNATE (Innate signaling networks in B cell antibody production: new targets for vaccine development)
This project identified a previously unknown population of neutrophils that surround splenic B cell follicles and are functionally different from circulating neutrophils. This is remarkable, considering that neutrophils were traditionally viewed as immune cells that only infiltrate tissues as a result of infection or inflammation. We found that splenic but not circulating neutrophils can deliver powerful antibody-inducing signals to a unique population of lymphocytes called marginal zone B cells. These B cells make protective antibodies against key pathogenicity factors (i.e. capsular polysaccharides) from a group of encapsulated bacteria typically causing pneumonitis, including Streptococcus pneumoniae. Such infections lead to more than 1.5 million deaths each year worldwide. Our research may stimulate the development of more effective vaccines against Streptococcus pneumoniae in subjects at higher risk of infection, including children aged <5 and adults aged >65. More in general, our findings led to a remarkable paradigm shift in immunology. Indeed, they indicate that neutrophils are not simple foot soldiers of our immune system, merely dedicated to a rapid but nonspecific clearance of microbes and cellular debris. Rather, neutrophils are sophisticated immune cells than may be harnessed to enhance highly specific antibody responses against different types of microbes, possibly including viruses. They also suggest that conditions associated with neutropenia may attenuate or impair antibody responses to vaccines. In general, we feel that our findings could lead to the development of new neutrophil-harnessing vaccine strategies against various pathogens, including new vaccine adjuvants.