Myeloid-Derived Suppressor Cells Evolve during Sepsis and Can Enhance or Attenuate the Systemic Inflammatory Response
| Autor: | Mohamed El Gazzar, Charles E. McCall, Laura Brudecki, Donald A. Ferguson |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
Adoptive cell transfer Myeloid Immunology Population Inflammation Biology Nitric Oxide Microbiology Gene Expression Regulation Enzymologic Proinflammatory cytokine Sepsis Mice medicine Animals Myeloid Cells education Mice Inbred BALB C education.field_of_study CD11b Antigen Arginase Cell Differentiation Bacterial Infections medicine.disease Adoptive Transfer Specific Pathogen-Free Organisms Disease Models Animal Interleukin 10 Infectious Diseases medicine.anatomical_structure Myeloid-derived Suppressor Cell Parasitology medicine.symptom |
| Zdroj: | Infection and Immunity. 80:2026-2034 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | Myeloid-derived suppressor cells (MDSCs) are a heterogeneous Gr1 + CD11b + population of immature cells containing granulocytic and monocytic progenitors, which expand under nearly all inflammatory conditions and are potent repressors of T-cell responses. Studies of MDSCs during inflammatory responses, including sepsis, suggest they can protect or injure. Here, we investigated MDSCs during early and late sepsis. To do this, we used our published murine model of cecal ligation and puncture (CLP)-induced polymicrobial sepsis, which transitions from an early proinflammatory phase to a late anti-inflammatory and immunosuppressive phase. We confirmed that Gr1 + CD11b + MDSCs gradually increase after CLP, reaching ∼88% of the bone marrow myeloid series in late sepsis. Adoptive transfer of early (day 3) MDSCs from septic mice into naive mice after CLP increased proinflammatory cytokine production, decreased peritoneal bacterial growth, and increased early mortality. Conversely, transfer of late (day 12) MDSCs from septic mice had the opposite effects. Early and late MDSCs studied ex vivo also differed in their inflammatory phenotypes. Early MDSCs expressed nitric oxide and proinflammatory cytokines, whereas late MDSCs expressed arginase activity and anti-inflammatory interleukin 10 (IL-10) and transforming growth factor β (TGF-β). Late MDSCs had more immature CD31 + myeloid progenitors and, when treated ex vivo with granulocyte-macrophage colony-stimulating factor (GM-CSF), generated fewer macrophages and dendritic cells than early MDSCs. We conclude that as the sepsis inflammatory process progresses, the heterogeneous MDSCs shift to a more immature state and from being proinflammatory to anti-inflammatory. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|