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Background The aim of the present study was to evaluate in vitro effects of exosomes derived from mesenchymal stem cells (MSCs) or tumor cells on recall-antigen-specific immune responses. Methods The exosomes were isolated from the supernatant of the cultures of the adipose-derived MSCs, and 4T1 cell line. The splenocytes isolated from experimental autoimmune encephalomyelitis (EAE) mice were utilized to evaluate the effects of exosomes on recall-antigen-specific responses. The expression of master regulators for T cell sub-types and the levels of their corresponding cytokines were evaluated. Results Treatment by disease-inducing peptide (MOG35–55) combined with MSC-EXO or by MOG+TEX enhanced the expression of Foxp3 as the master regulator for Treg cells; by comparing with splenocytes which were treated by MOG. Nonetheless, the production of IL-10 and TGF-β were increased only in splenocytes treated by MOG+TEX. Additionally, treatments of splenocytes by MOG+TEX and MOG+MSC-EXO decreased the expression of Tbx21 and Gata3, as the master regulator for T helper (TH)1 and TH2 responses. However, the IFN-γ level did not decrease. The expression of Rorc and Elf4, which are the activator and inhibitor for differentiation of TH17 respectively were increased after splenocytes was treated by MOG+TEX. However, a reduction in Rorc and Elf4 levels was observed when splenocytes were treated by MOG+MSC-EXO. Indeed, the concentration of IL-17 did not alter significantly following the treatment by MOG+exosomes. Conclusion It was ultimately attained that TEX and MSC-EXO utilized various mechanisms to modulate the recall immune responses. TEX was more potent than MSC-EXO to induce regulatory responses by upregulating the production of Foxp3, IL-10, and TGF-β.

MiR-155 could act as a key modulator of different aspects of immune system including Th1 responses. In this study, we designed chitosan nanoparticles containing miR-155-expressing plasmid and explored their effects as an adjuvant to enhance Th1 responses for potential future application against intracellular pathogens.Nanoparticles were formulated by complex coacervation method and characterized for physicochemical and functional characteristics. Transfection efficiency in Raw 264.7 cells, effects on miR-155 target genes and NO production were evaluated. The prepared nanoparticles were co-administered as an adjuvant with ovalbumin to immunize mice and finally production of IFN-γ and IL-4 were measured by ELISA in splenocyte recall responses.The prepared nanoparticles had the mean size of 244 nm and zeta potential of +17 mV, respectively. Electrophoresis analysis indicated the high capability of nanoparticles to protect the plasmid from DNaseI degradation. Furthermore, nanoparticles showed an appropriate transfection efficiency in Raw 264.7 cells and could downregulate the expression of miR-155 target genes and also upregulate NO production. In vivo immunization examinations revealed successful shift of T cell responses toward Th1.Our data suggests the high potential of chitosan nanoparticles containing miR-155-expressing plasmid as an adjuvant for significantly enhanced Th1-biased immune responses upon immunization with a given antigen.

Chitin and chitosan microparticles (MPs) are important immune system stimulators. The aim of this study was to evaluate the protective effects of these compounds in comparison with each other against Leishmania infection in BALB/c mice infected with Leishmania major (L. major). Female BALB/c mice were injected subcutaneously with 2×10(5) promastigotes. Chitin and/or chitosan MPs (

Chitin and its some derivatives are known to be non-allergic and non-toxic substances. It has been shown that chitin microparticles have immunomodulatory activities. In the present study, we investigated the in vivo immunomodulatory activities of chitin microparticles (CMPs) on Leishmania major -infected BALB/c mice. BALB/c mice were infected with L. major promastigotes at their base of the tail. CMPs (100 μg/100 μl) were injected into the site of infection from 3 days before to 2 or 8 weeks after infection at two-day intervals. Cytokine concentrations (TNF-α, IFN-γ, IL-5 and IL-10) were measured using ELISA assays. Compared to the untreated group, production of TNF-α was significantly elevated in the CMPs-treated group. Moreover, the IFN-γ/IL-5 ratio was significantly elevated in CMPs-treated infected mice ( P = 0.023). Notably, the concentration of IL-10 was higher in CMPs-treated mice. These results showed that CMPs have in vivo immunomodulatory effects via the production of IFN-γ and IL-10. We also measured the onset and size of lesions in both treated and untreated mice. The average times taken for the onset of the lesion formation were 35 and 29 days for CMPs-treated and untreated mice ( P = 0.023), respectively. The mean size of the lesions was smaller in CMPs-treated group. Our study serves as a basis for future investigations on the application of CMPs as a prophylactic (vaccine adjuvant) and/or therapeutic modality against leishmaniasis.

Background Chitin microparticles (CMPs) are found to be potent macrophage stimulators; however, their immunomodulatory effects on the parasite-infected macrophages have not yet been studied. To address this issue, we used a Leishmania major -infected murine macrophage model and characterized the regulatory effects of CMPs on the parasite-infected cells. Methods Mouse peritoneal macrophages were prepared and infected with L. major (MRHO/IR/1975/ER) standard strain. Following cell treatment with CMPs (500 μg/mL) for 48 h, percent of infected macrophages was determined by Giemsa staining and compared with untreated cells. To find the potential mechanisms of the activity of CMPs, TNF-α and accumulated nitrite in the culture supernatants of the treated and untreated cells were also measured by ELISA and colorimetric Griess assays, respectively. Results According to the obtained results, chitin microparticles reduced the ex vivo parasite infectivity by ∼12%. However, this inhibitory effect was not directly related to the increased biosynthesis and release of nitric oxide (NO) by macrophages. Instead, we observed a significant increase in the level of TNF-α secretion due to cell treatment with CMPs. Interestingly, this overexpression of TNF-α did not impair cell viability, suggesting the anti-apoptotic effects of the CMPs. Conclusions These findings show that chitin microparticles have immunomodulatory effects on L. major- infected macrophages and further provide motivations for future studies on their in vivo effects.

Background GB virus-C (GBV-C) is a flavivirus that probably influences HIV infection-associated disease among HIV/GBV-C coinfected patients and inhibits the progression of HIV infection to AIDS. To address the possibility of immune-modulating effects of GBV-C coinfection in HIV patients, we evaluated interferon-producing cells in HIV/GBV-C coinfected patients and compared them to HIV-infected patients. Methods We performed a pilot study to enumerate interferon-producing cell count by two-color flow cytometric analysis and also for determining the frequency of ongoing GBV-C and HCV infection among patients infected with HIV. Then, 83 asymptomatic HIV-positive patients were considered for evaluation of interferon-producing cells. Eighty three patients were stratified in four groups according to the HCV and GBV-C infection status: patients infected with HCV and GBV-C (GBV-C+/HCV+), patients infected with GBV-C but not with HCV (GBV-C+/HCV−), patients infected with HCV but not with GBV-C (GBV-C−/HCV+), and patients not infected by GBV-C and HCV (GBV-C-/HCV−). Results GBV-C was detected in plasma samples from 15.5% of HIV-infected patients and the frequency of HCV infection was 47.5%. Interferon-producing cells in GBV-C coinfected individuals revealed a wider range of numbers; however, there was no significant difference in the interferon-producing cell count among HIV-infected individuals. Conclusions It does not appear that GBV-C coinfection affects generation or redistribution of interferon-producing cells in HIV-infected patients with relatively intact immune system.