19Staphylococcus aureus (S. aureus) is a challenging human pathogen due to its ability to evade the 20 immune system and resist multidrug antibiotics. These evasive strategies lead to chronic and re-21 current infections. Many studies have documented that during chronic infections Myeloid Derived 22 Suppressor Cells (MDSCs) exert immunosuppressive mechanisms on T cells. A mathematical 23 model explains how the steady state of chronic infection can be disturbed and suggests therapeutic 24 strategies to clear the infection. Model-driven suggestions were tested experimentally and con-25 firmed complete clearance of S. aureus chronic infection. 26 Keywords 27 Myeloid Derived Suppressor Cells, MDSCs, Staphylococcus aureus, chronic infection, mathematical model, 28 therapy, cure, heat-killed cells 29Staphylococcus aureus (S. aureus) is a bacterial human pathogen colonizing 20%-30% of the world pop-30 ulation and responsible for the genesis of nosocomial-acquired and community-acquired bacterial infections. 31 Colonization by S. aureus is typically asymptomatical, implying an equilibrated state between host and bac-32 terium. However, the bacterium can become opportunistic often post-surgery or after implantation of medical 33 devices and can cause skin and soft tissue infections, such as dermatitis, impetigo, and cellulitis 1 , as well as 34 life-threatening conditions like pneumonia and chronic osteomyelitis 2 . Additionally, individuals with immune 35 deficiencies are more susceptible to S. aureus infections. The pathogen constitutes a serious problem in clin-36 ics worldwide because it uses multiple mechanisms to persist in the host. These include strategies of bacterial 37 1 evasion, multi-drug antibiotic resistance, immunosuppression 3 or manipulation of the host's immune regulatory 38 mechanisms, 4;5 which lead to chronic and difficult-to-treat infections. 39Typically, immunosuppression is achieved via regulatory T cells (Tregs), T cell lysis, regulatory B cells 40 (Bregs) 6 , and Myeloid-Derived Suppressor Cells (MDSCs). In the case of S. aureus chronic infections, immuno-41 suppression is not attributed to Bregs, tolerogenic dendritic cells, nor Tregs 7 . Treg-depletion has only a minor 42 effect, whereas T-cell proliferation remains inhibited despite the absence of B220 + and CD11c + cells 7 . Never-43 theless, T-cell suppression in chronically infected mice has been associated with the expansion of monocytic-like 44 (CD11b + Ly6C + Ly6G low phenotype), neutrophilic-like (CD11b + Ly6C low Ly6G + phenotype) and eosonophilic-45 like (CD11b + Ly6C low Ly6G low phenotype) MDSCs 7;8;9;10;11 , affirming the dominant immunosuppressive role of 46 MDSCs during chronic S. aureus infections. 47MDSCs constitute a heterogeneous population of immature myeloid cells, which exert their suppressive 48 effect on T cells by producing reactive oxygen species, nitric oxide, arginase, and inducible nitric oxide syn-49 thase. Significant MDSC expansion and the consequent immunosuppressive effect were reported in long-lasting 50 p...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.