Expansion of myeloid-derived suppressor cells with arginase activity lasts longer in aged than in young mice after CpG-ODN plus IFA treatment

Abstract

As we age, the homeostatic function of many systems in the body, such as the immune function declines, which in turn contributes to augment susceptibility to disease. Here we describe that challenging aged mice with synthetic oligodeoxynucleotides containing unmethylated cytosine guanine motifs (CpG-ODN) emulsified in incomplete Freund's adjuvant (IFA), (CpG-ODN+IFA) an inflammatory stimulus, led to the expansion of CD11b+Gr1+ myeloid cells with augmented expression of CD124 and CD31. These myeloid cells lasted longer in the spleen of aged mice than in their younger counterparts after CpG-ODN+IFA treatment and were capable of suppressing T cell proliferative response by arginase induction. Myeloid cells from aged CpG-ODN+IFA-treated mice presented increased arginase-1 expression and enzyme activity. In addition, we found a different requirement of cytokines for arginase induction according to mice age. In myeloid cells from young treated mice, arginase-1 expression and activity is induced by the presence of each IL-4 or IL-6 in their extracellular medium, unlike myeloid cells from aged treated mice which need the presence of both IL-4 and IL-6 together for arginase induction and suppressor function.

Comprehensive Analysis of the Neutrophil‐to‐Lymphocyte Ratio for Preoperative Prognostic Prediction Nomogram in Gastric Cancer

“…The granulocytic myeloid-derived suppressor cells (g-MDSC) are morphologically similar to regular neutrophils except for their high density and specific markers [38,39]. The g-MDSC suppress the tumor immune response, while their proportion to overall neutrophils increases by age [40][41][42]. Aging changes lymphocyte profiles: T cells shift from naive cells to memory cells; B cells decrease and NK cells increase in the blood [43][44][45].…”

Myeloid-derived suppressor cells and vaccination against pathogens

“…(2015) described that MDSCs expanded in aged mice after immunization with CpG-ODN emulsified with Freund´s adjuvant lasted longer in the spleen of aged mice than in their younger counterparts. CD11b+ Gr1+ cells highly express other surface proteins, such as CD124 and CD31, and were capable of suppressing T cell proliferative response by arginase induction ( Harman et al., 2015 ).…”

Myeloid-Derived Suppressor Cells: Not Only in Tumor Immunity

“…Aged mice have even lower levels of CD62L on their naive T cells because they have higher levels of MDSCs. Additionally, older mice have a reduced ability to clear MDSCs following experimentally induced expansion (60). Similarly, in humans, compared to young adults (<60 years old), older community-dwelling individuals (61–76 years old) and the frail, institutionalized elderly (67–99 years old) exhibit significantly higher peripheral blood levels of CD33 + HLA-DR-negative MDSCs, especially the CD11b + CD15 + subset (5).…”