PD-1 Suppresses Protective Immunity to Streptococcus pneumoniae through a B Cell-Intrinsic Mechanism.

J Immunol. 2015 Jan 26. pii: 1401673. [Epub ahead of print]

PD-1 Suppresses Protective Immunity to Streptococcus pneumoniae through a B Cell-Intrinsic Mechanism.

McKay JT1, Egan RP1, Yammani RD1, Chen L2, Shin T3, Yagita H4, Haas KM5.

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Abstract

Despite the emergence of the programmed cell death 1 (PD-1):PD-1 ligand (PD-L) regulatory axis as a promising target for treating multiple human diseases, remarkably little is known about how this pathway regulates responses to extracellular bacterial infections. We found that PD-1-/- mice, as well as wild-type mice treated with a PD-1 blocking Ab, exhibited significantly increased survival against lethal Streptococcus pneumoniae infection following either priming with low-dose pneumococcal respiratory infection or S. pneumoniae-capsular polysaccharide immunization. Enhanced survival in mice with disrupted PD-1:PD-L interactions was explained by significantly increased proliferation, isotype switching, and IgG production by pneumococcal capsule-specific B cells. Both PD-L, B7-H1 and B7-DC, contributed to PD-1-mediated suppression of protective capsule-specific IgG. Importantly, PD-1 was induced on capsule-specific B cells and suppressed IgG production and protection against pneumococcal infection in a B cell-intrinsic manner. To our knowledge, these results provide the first demonstration of a physiologic role for B cell-intrinsic PD-1 expression in vivo. In summary, our study reveals that B cell-expressed PD-1 plays a central role in regulating protection against S. pneumoniae, and thereby represents a promising target for bolstering immunity to encapsulated bacteria.

Copyright © 2015 by The American Association of Immunologists, Inc.

PMID: 25624454 [PubMed - as supplied by publisher]