Mesenchymal stem cells alter macrophage immune responses to Leishmania major infection in both susceptible and resistance mice

Safura Dameshghi; Ahmad Zavaran-Hosseini; Sara Soudi; Fatemeh Jalali Shirazi; Shahrzad Nojehdehi; Seyed Mahmoud Hashemi

doi:10.1016/j.imlet.2015.12.002

Mesenchymal stem cells alter macrophage immune responses to Leishmania major infection in both susceptible and resistance mice

Immunol Lett. 2016 Feb:170:15-26. doi: 10.1016/j.imlet.2015.12.002. Epub 2015 Dec 15.

Authors

Safura Dameshghi¹, Ahmad Zavaran-Hosseini², Sara Soudi³, Fatemeh Jalali Shirazi¹, Shahrzad Nojehdehi⁴, Seyed Mahmoud Hashemi⁵

Affiliations

¹ Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
² Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: [email protected].
³ Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: [email protected].
⁴ Immunology Department, Stem Cell Technology Research Center, Tehran, Iran.
⁵ Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

PMID: 26703818
DOI: 10.1016/j.imlet.2015.12.002

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.

Keywords: Leishmania major; Macrophage; Mesenchymal stem cell; Mouse strain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Coculture Techniques
Cytokines / metabolism
Disease Models, Animal
Disease Resistance*
Disease Susceptibility*
Female
Immunophenotyping
Inflammation Mediators / metabolism
Leishmania major / immunology*
Leishmaniasis, Cutaneous / immunology*
Leishmaniasis, Cutaneous / parasitology
Macrophages / immunology*
Macrophages / metabolism
Macrophages / parasitology
Macrophages, Peritoneal / immunology
Macrophages, Peritoneal / metabolism
Macrophages, Peritoneal / parasitology
Mesenchymal Stem Cells / immunology*
Mesenchymal Stem Cells / metabolism
Mice
Nitric Oxide / metabolism
Phagocytosis
Phenotype

Substances

Cytokines
Inflammation Mediators
Nitric Oxide