RT Journal Article
SR Electronic
T1 PI3Kδ hyper-activation promotes the development of B cells that exacerbate <em>Streptococcus pneumoniae</em> infection in an antibody-independent manner
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 280651
DO 10.1101/280651
A1 Anne-Katrien Stark
A1 Anita Chandra
A1 Krishnendu Chakraborty
A1 Rafeah Alam
A1 Valentina Carbonaro
A1 Jonathan Clark
A1 Srividya Sriskantharajah
A1 Glyn Bradley
A1 Alex G. Richter
A1 Edward Banham-Hall
A1 Menna R. Clatworthy
A1 Sergey Nejentsev
A1 J. Nicole Hamblin
A1 Edith M. Hessel
A1 Alison M. Condliffe
A1 Klaus Okkenhaug
YR 2018
UL http://biorxiv.org/content/early/2018/03/18/280651.abstract
AB Streptococcus pneumoniae is a major cause of pneumonia and a leading cause of death world-wide. Antibody-mediated immune responses can offer protection against repeated exposure to S. pneumoniae, yet vaccines only offer partial protection. Patients with Activated PI3Kδ Syndrome (APDS) are highly susceptible to S. pneumoniae. We generated a conditional knockin mouse model of this disease and identified a CD19+B220− B cell subset that is induced by PI3Kδ signaling, is resident in the lungs, and which promotes increased susceptibility to S. pneumoniae during the early phase of infection via an antibody-independent mechanism. We show that an inhaled PI3Kδ inhibitor improves survival rates following S. pneumoniae infection in wild-type mice and in mice with activated PI3Kδ. These results suggest that a subset of B cells in the lung can promote the severity of S. pneumoniae infection, representing a novel therapeutic target.