Marine FungusAspergillus chevalieriTM2-S6 Extract Protects Skin Fibroblasts from Oxidative Stress
MARINE DRUGS
Authors: Letsiou, Sophia; Bakea, Artemis; Le Goff, Geraldine; Lopes, Philippe; Gardikis, Konstantinos; Weis, Michal; Benayahu, Yehuda; Ouazzani, Jamal
Abstract
The strainAspergillus chevalieriTM2-S6 was isolated from the spongeAxinellaand identified according to internal transcribed spacer (ITS) molecular sequence homology withAspergillusspecies from the sectionRestricti. The strain was cultivated 9 days on potato dextrose broth (PDB), and the medium evaluated as antioxidant on primary normal human dermal fibroblasts (NHDF). The cultivation broth was submitted to sterile filtration, lyophilized and used without any further processing to give theAspergillus chevalieriTM2-S6 cultivation broth ingredient named ACBB. ACCB contains two main compounds: tetrahydroauroglaucin and flavoglaucin. Under oxidative stress, ACCB showed a significant promotion of cell viability. To elucidate the mechanism of action, the impact on a panel of hundreds of genes involved in fibroblast physiology was evaluated. Thus, ACCB stimulates cell proliferation (VEGFA, TGFB3), antioxidant response (GPX1, SOD1, NRF2), and extracellular matrix organization (COL1A1, COL3A1, CD44, MMP14). ACCD also reduced aging (SIRT1, SIRT2, FOXO3). These findings indicate thatAspergillus chevalieriTM2-S6 cultivation broth exhibits significant in vitro skin protection of human fibroblasts under oxidative stress, making it a potential cosmetic ingredient.
LUNG MEMORY T-CELL RESPONSE IN MICE FOLLOWING INTRANASAL IMMUNIZATION WITH INFLUENZA VECTOR EXPRESSING MYCOBACTERIAL PROTEINS
INFEKTSIYA I IMMUNITET
Authors: Shurygina, A-P S.; Zabolotnykh, N., V; Vinogradova, T., I; Vasilyev, K. A.; Buzitskaya, Zh, V; Stukova, M. A.
Abstract
Improving specific prevention of tuberculosis continues to be a top priority in phthisiology. "Prime-boost" vaccination schemes aim to maintain adequate levels of specific immunity while forming long-term protection. They are based on sequential use of BCG vaccine and new vaccine candidates expressing protective mycobacterial proteins. The development of new tuberculosis prevention approaches requires an understanding of how the anti-tuberculosis immune response forms and which mechanisms provide TB protection. Since tuberculosis is an airborne infection, vaccine effectiveness largely depends on mucosal immunity based on the formation of long-lived, functionally-active memory T-lymphocytes in the respiratory tract. We have previously shown that the influenza vector expressing ESAT-6 and Ag85A mycobacterial proteins (Flu/ESAT-6_Ag85A) in vaccination scheme of intranasal boost immunization resulted in significant increase of BCG's protective effect according to key indicators aggregate data in experimental tuberculosis infection. The aim of this work was to study the effect of intranasal immunization with the Flu/ESAT-6_Ag85A influenza vector on the formation of antigen-specific central and effector memory T cells and the cytokine-producing activity of effector T cells (TEM) in BCG standard and "BCG prime-influenza vector boost" vaccination schemes in mice. Intranasal immunization with the influenza vector has been shown to increase the proportion of antigen-specific CD4(+) central memory T cells (TCM) in the pool of activated lymphocytes of lung and spleen reaching significant differences from the BCG group in the percentage of spleen CD4(+) TCM (p < 0.01). In contrast to BCG, vaccination with the studied vaccine candidate was accompanied by accumulation of highly differentiated CD8 effector cells in lung, the target organ during tuberculosis infection. Comparative evaluation of the cell-mediated, post-vaccine immune response after immunization with influenzavector-based vaccine candidate (intranasal/mucosal) or BCG vaccine (subcutaneous) showed advantages in the mucosal group: in formation of functionally active subpopulations of effector CD4 and CD8 T lymphocytes (CD44(high)CD62L(low)) in lungs secreting IL-2 as well as polyfunctional cells capable of coproducing two cytokines (IFN gamma/TNF alpha or IFN gamma/IL-2) or three cytokines (IFN gamma/TNF alpha/IL-2). Due to their more pronounced effector function, polyfunctional T-lymphocytes can be considered to be potential immunological markers of protective immunity in tuberculosis.