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

  • McKay J
  • Egan R
  • Yammani R
  • et al.
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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.

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APA

McKay, J. T., Egan, R. P., Yammani, R. D., Chen, L., Shin, T., Yagita, H., & Haas, K. M. (2015). PD-1 Suppresses Protective Immunity to Streptococcus pneumoniae through a B Cell–Intrinsic Mechanism. The Journal of Immunology, 194(5), 2289–2299. https://doi.org/10.4049/jimmunol.1401673

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