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Tolerogenic probiotics Lactobacillus delbrueckii and Lactobacillus rhamnosus promote anti-inflammatory profile of macrophages-derived monocytes of newly diagnosed patients with systemic lupus erythematosus
Authors:Zahra Javanmardi  Mahmoud Mahmoudi  Houshang Rafatpanah  Zahra Rezaieyazdi  Abbas Shapouri-Moghaddam  Parisa Ahmadi  Samaneh Mollazadeh  Nafiseh Sadat Tabasi  Seyed-Alireza Esmaeili
Affiliation:1. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran;2. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;3. Immunology Research Centre, Division of Inflammation and Inflammatory Diseases, Mashhad University of Medical Sciences, Mashhad, Iran;4. Rheumatic Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;5. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;6. Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran

Abstract:Systemic lupus erythematosus (SLE) is known as an autoimmune disorder that is characterized by the breakdown of self-tolerance, resulting in disease onset and progression. Macrophages have been implicated as a factor in the development of SLE through faulty phagocytosis of dead cells or an imbalanced M1/M2 ratio. The study aimed to investigate the immunomodulatory effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on M1 and M2 macrophages in new case lupus patients. For this purpose, blood monocytes were collected from lupus patients and healthy people and were cultured for 5 days to produce macrophages. For 48 h, the macrophages were then cocultured with either probiotics or lipopolysaccharides (LPS). Flow cytometry and real-time polymerase chain reaction were then used to analyze the expression of cluster of differentiation (CD) 14, CD80, and human leukocyte antigen – DR (HLADR) markers, as well as cytokine expression (interleukin [IL]1-β, IL-12, tumor necrosis factor α [TNF-α], IL-10, and transforming growth factor beta [TGF-β]). The results indicated three distinct macrophage populations, M0, M1, and M2. In both control and patient-derived macrophage-derived monocytes (MDMs), the probiotic groups showed a decrease in CD14, CD80, and HLADR expression compared to the LPS group. This decrease was particularly evident in M0 and M2 macrophages from lupus patients and M1 macrophages from healthy subjects. In addition, the probiotic groups showed increased levels of IL-10 and TGF-β and decreased levels of IL-12, IL1-β, and TNF-α in MDMs from both healthy and lupus subjects compared to the LPS groups. Although there was a higher expression of pro-inflammatory cytokines in lupus patients, there was a higher expression of anti-inflammatory cytokines in healthy subjects. In general, L. delbrueckii and L. rhamnosus could induce anti-inflammatory effects on MDMs from both healthy and lupus subjects.
Keywords:Lactobacillus delbrueckii  Lactobacillus rhamnosus  macrophage  M0/M1/M2 macrophages  probiotic  systemic lupus erythematosus
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