Bacterial c-di-GMP affects hematopoietic Stem/progenitors and their niches through STING

Hiroshi Kobayashi, Chiharu I. Kobayashi, Ayako Nakamura-Ishizu, Daiki Karigane, Hiroshi Haeno, Kimiyo N. Yamamoto, Taku Sato, Toshiaki Ohteki, Yoshihiro Hayakawa, Glen N. Barber, Mineo Kurokawa, Toshio Suda, Keiyo Takubo

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Upon systemic bacterial infection, hematopoietic stem and progenitor cells (HSPCs) migrate to the periphery in order to supply a sufficient number of immune cells. Although pathogen-associated molecular patterns reportedly mediate HSPC activation, how HSPCs detect pathogen invasion invivo remains elusive. Bacteria use the second messenger bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) for a variety of activities. Here, we report that c-di-GMP comprehensively regulated both HSPCs and their niche cells through an innate immune sensor, STING, thereby inducing entry into the cell cycle and mobilization of HSPCs while decreasing the number and repopulation capacity of long-term hematopoietic stem cells. Furthermore, we show that type I interferon acted as a downstream target of c-di-GMP to inhibit HSPC expansion in the spleen, while transforming growth factor-β was required for c-di-GMP-dependent splenic HSPC expansion. Our results define machinery underlying the dynamic regulation of HSPCs and their niches during bacterial infection through c-di-GMP/STING signaling.

Original languageEnglish
Pages (from-to)71-84
Number of pages14
JournalCell Reports
Volume11
Issue number1
DOIs
Publication statusPublished - Apr 7 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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