Immature myeloid Gr-1+ CD11b+ cells from lipopolysaccharide-immunosuppressed mice acquire inhibitory activity in the bone marrow and migrate to lymph nodes to exert their suppressive function.

LANDONI VERÓNICA INÈS; MARTIRE GRECO D; RODRIGUEZ RODRIGUES, NAHUEL; CHIARELLA P; SCHIERLOH P; ISTURIZ M.A; FERNANDEZ G.C

CLINICAL SCIENCE (LONDON, ENGLAND : 1979)

PORTLAND PRESS LTD

Lugar: Londres; Año: 2016

0143-5221

Secondary infections due to post-sepsis immunosuppression are a major cause of death in septic patients. Repetitive inoculation of increasing doses of lipopolysaccharide (LPS) to mice mimics the immunosuppression associated to sepsis. Myeloid-derived suppressor cells (MDSCs, Gr-1+ CD11b+) are considered a major component of the immunosuppressive network interfering with T-cell responses in many pathological conditions. We used LPS-immunosuppressed (IS) mice to address whether MDSC acquired their suppressive ability in the bone marrow (BM) and if they were able to migrate to lymph nodes (LN) to exert their suppressive function. Our results showed that Gr-1+ CD11b+ cells of IS mice had the potential to inhibit T cell proliferation already in the BM. Moreover, soluble factors present in the BM from IS mice were responsible for inducing this inhibitory ability in control BM cells. Additionally, migration of Gr-1+ CD11b+ to LN in vivo was maximal when cells obtained from BM of IS mice were inoculated in an immunosuppressed context. In this regard, we found chemoattractant activity in cell-free LN extracts (LNE) from IS mice and an increased expression of the LN-homing chemokine receptor CCR7 in IS BM Gr-1+ CD11b+ cells. These results indicate that Gr-1+ CD11b+ found in BM from IS mice acquire their suppressive activity in the same niche where they are generated and migrate to LN to exert their inhibitory role. A better understanding of MDSC generation and/or regulation of factors able to induce their inhibitory function may provide new and more effective tools for the treatment of sepsis-associated immunosuppression.