MiR-155-regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis.
|Title||MiR-155-regulated molecular network orchestrates cell fate in the innate and adaptive immune response to Mycobacterium tuberculosis.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Rothchild AC, Sissons JR, Shafiani S, Plaisier C, Min D, Mai D, Gilchrist M, Peschon J, Larson RP, Bergthaler A, Baliga NS, Urdahl KB, Aderem A|
|Journal||Proc Natl Acad Sci U S A|
|Date Published||2016 Oct 11|
The regulation of host-pathogen interactions during Mycobacterium tuberculosis (Mtb) infection remains unresolved. MicroRNAs (miRNAs) are important regulators of the immune system, and so we used a systems biology approach to construct an miRNA regulatory network activated in macrophages during Mtb infection. Our network comprises 77 putative miRNAs that are associated with temporal gene expression signatures in macrophages early after Mtb infection. In this study, we demonstrate a dual role for one of these regulators, miR-155. On the one hand, miR-155 maintains the survival of Mtb-infected macrophages, thereby providing a niche favoring bacterial replication; on the other hand, miR-155 promotes the survival and function of Mtb-specific T cells, enabling an effective adaptive immune response. MiR-155-induced cell survival is mediated through the SH2 domain-containing inositol 5-phosphatase 1 (SHIP1)/protein kinase B (Akt) pathway. Thus, dual regulation of the same cell survival pathway in innate and adaptive immune cells leads to vastly different outcomes with respect to bacterial containment.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|
|PubMed Central ID||PMC5068277|
|Grant List||R01 AI032972 / AI / NIAID NIH HHS / United States |
HHSN272201300006C / AI / NIAID NIH HHS / United States
U19 AI100627 / AI / NIAID NIH HHS / United States
R01 AI025032 / AI / NIAID NIH HHS / United States
R01 AI076327 / AI / NIAID NIH HHS / United States
U19 AI106761 / AI / NIAID NIH HHS / United States