Unknown

Dataset Information

0

Lymphotoxin-mediated crosstalk between B cells and splenic stroma promotes the initial type I interferon response to cytomegalovirus.


ABSTRACT: Toll-like receptor (TLR)-dependent pathways control the production of IFNalphabeta, a key cytokine in innate immune control of viruses including mouse cytomegalovirus (MCMV). The lymphotoxin (LT) alphabeta-LTbeta receptor signaling pathway is also critical for defense against MCMV and thought to aid in the IFNbeta response. We find that upon MCMV infection, mice deficient for lymphotoxin (LT)alphabeta signaling cannot mount the initial part of a biphasic IFNalphabeta response, but show normal levels of IFNalphabeta during the sustained phase of infection. Significantly, the LTalphabeta-dependent, IFNalphabeta response is independent of TLR signaling. B, but not T, cells expressing LTbeta are essential for promoting the initial IFNalphabeta response. LTbetaR expression is required strictly in splenic stromal cells for initial IFNalphabeta production to MCMV and is dependent upon the NF-kappaB-inducing kinase (NIK). These results reveal a TLR-independent innate host defense strategy directed by B cells in communication with stromal cells via the LTalphabeta cytokine system.

SUBMITTER: Schneider K 

PROVIDER: S-EPMC2703178 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Lymphotoxin-mediated crosstalk between B cells and splenic stroma promotes the initial type I interferon response to cytomegalovirus.

Schneider Kirsten K   Loewendorf Andrea A   De Trez Carl C   Fulton James J   Rhode Antje A   Shumway Heather H   Ha Sukwon S   Patterson Ginelle G   Pfeffer Klaus K   Nedospasov Sergei A SA   Ware Carl F CF   Benedict Chris A CA  

Cell host & microbe 20080201 2


Toll-like receptor (TLR)-dependent pathways control the production of IFNalphabeta, a key cytokine in innate immune control of viruses including mouse cytomegalovirus (MCMV). The lymphotoxin (LT) alphabeta-LTbeta receptor signaling pathway is also critical for defense against MCMV and thought to aid in the IFNbeta response. We find that upon MCMV infection, mice deficient for lymphotoxin (LT)alphabeta signaling cannot mount the initial part of a biphasic IFNalphabeta response, but show normal le  ...[more]

Similar Datasets

| S-EPMC5343017 | biostudies-literature
| S-EPMC10100850 | biostudies-literature
| S-EPMC7970251 | biostudies-literature
| S-EPMC5934403 | biostudies-literature
| S-EPMC4936157 | biostudies-literature
| S-EPMC5147843 | biostudies-literature
| S-EPMC4081445 | biostudies-literature
| S-EPMC4695340 | biostudies-literature
| S-EPMC1386719 | biostudies-literature
| S-EPMC8214757 | biostudies-literature