TY - JOUR
T1 - Bacterial c-di-GMP affects hematopoietic Stem/progenitors and their niches through STING
AU - Kobayashi, Hiroshi
AU - Kobayashi, Chiharu I.
AU - Nakamura-Ishizu, Ayako
AU - Karigane, Daiki
AU - Haeno, Hiroshi
AU - Yamamoto, Kimiyo N.
AU - Sato, Taku
AU - Ohteki, Toshiaki
AU - Hayakawa, Yoshihiro
AU - Barber, Glen N.
AU - Kurokawa, Mineo
AU - Suda, Toshio
AU - Takubo, Keiyo
N1 - Funding Information:
We thank T. Taniguchi and H. Negishi for providing Irf3 −/− and Irf3 −/− : Irf7 −/− mice; A. Shibuya and N. Totsuka for advice on the CeLP procedure; M. Suematsu and T. Hishiki for fluorescence-activated cell sorting analysis and c-di-GMP characterization; T. Muraki, K. Endo, M. Katabami-Maie, and T. Hirose for technical support and laboratory management; and R. Goitsuka for providing mice. K.T. was supported by the Tenure-Track Program at the Sakaguchi Laboratory and in part by a MEXT Grant-in-Aid for Young Scientists (A), a grant from the National Center for Global Health and Medicine , and a grant from the Japan Science and Technology Agency (JST), Core Research for Evolution Science and Technology (CREST) . T. Suda and K.T. were supported in part by a MEXT Grant-in-Aid for Scientific Research (A) and a MEXT Grant-in-Aid for Scientific Research on Innovative Areas. H.K., C.I.K., and A.N.-I. are research fellows of the Japan Society for the Promotion of Science .
Publisher Copyright:
© 2015 The Authors.
PY - 2015/4/7
Y1 - 2015/4/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2015.02.066
DO - 10.1016/j.celrep.2015.02.066
M3 - Article
C2 - 25843711
AN - SCOPUS:84927697978
SN - 2211-1247
VL - 11
SP - 71
EP - 84
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -