title: Mesenchymal stem cells alter macrophage immune responses to Leishmania major infection in both susceptible and resistance mice.
abstract: Mesenchymal stem cells (MSCs) are attracted to inflammation site and switch immune system to modulate inflammatory responses. This ability makes MSCs the best candidate cells for stem cell therapy of infection diseases. Therefore, we aimed to evaluate the modulatory effect of adipose-derived MSCs (AD-MSCs) on macrophages in Leishmania (L.) major infection. Macrophages and MSCs were isolated from both susceptible (BALB/c) and resistance (C57BL/6) strains. After co-culture of AD-MSCs with macrophages using a transwell system, we assessed MSCs-educated macrophage responses to L. major infection. Our results indicated suppression in levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) of MSCs co-cultured macrophages in response to L. major infection. To clarify the effects of this suppression on inflammatory conditions, TNF-α/IL-10 ratio was calculated, indicating an increase in TNF-α/IL-10 ratio in MSCs co-cultured groups. The higher TNF-α/IL-10 ratio was observed in BALB/c macrophages co-cultured with BALB/c MSCs. Nitric oxide (NO) assay presented a significant reduction in the supernatant of all MSCs co-cultured groups compared to control. We observed a significant reduction in phagocytosis of MSCs co-cultured groups in response to L. major infection without any significant differences in the phagocytic index. In conclusion, our results represented a new spectrum of immunomodulation induced by MSCs co-cultured with macrophages in response to L. major infection. The magnitude of immunoregulation was different between BALB/c and C57BL/6 strains. Our findings also showed that MSCs exerted potential effect of M1 polarization due to unequal decrease in levels of TNF-α and IL-10 when we considered TNF-α and IL-10as representatives of M1 and M2 phenotypes, respectively. Induction of inflammatory cytokine milieu and reduction in level of IL-10 provides a new hope for stem cell therapy of leishmaniasis in susceptible models.
authors.affiliation: Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Safura
authors.initials: S
authors.lastname: Dameshghi
authors.affiliation: Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: zavarana@modares.ac.ir.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Zavaran-Hosseini
authors.affiliation: Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: Soudi@modares.ac.ir.
authors.forename: Sara
authors.initials: S
authors.lastname: Soudi
authors.affiliation: Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Fatemeh Jalali
authors.initials: FJ
authors.lastname: Shirazi
authors.affiliation: Immunology Department, Stem Cell Technology Research Center, Tehran, Iran.
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Nojehdehi
authors.affiliation: Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Mahmoud
authors.initials: SM
authors.lastname: Hashemi
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D060467:Disease Resistance; D004198:Disease Susceptibility; D005260:Female; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis; D010641:Phenotype
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D009569:Nitric Oxide
keywords: Leishmania major; Macrophage; Mesenchymal stem cell; Mouse strain