Mucosal Therapy of Multi-Drug Resistant Tuberculosis With IgA and Interferon-gamma
FRONTIERS IN IMMUNOLOGY
Authors: Tran, Andy C.; Diogo, Gil R.; Paul, Matthew J.; Copland, Alastair; Hart, Peter; Mehta, Nickita; Irvine, Edward. B.; Mussa, Tufaria; Drake, Pascal M. W.; Ivanyi, Juraj; Alter, Galit; Reljic, Rajko
Abstract
New evidence has been emerging that antibodies can be protective in various experimental models of tuberculosis. Here, we report on protection against multidrug-resistant Mycobacterium tuberculosis (MDR-TB) infection using a combination of the human monoclonal IgA 2E9 antibody against the alpha-crystallin (Acr, HspX) antigen and mouse interferon-gamma in mice transgenic for the human IgA receptor, CD89. The effect of the combined mucosal IgA and IFN-gamma; treatment was strongest (50-fold reduction) when therapy was applied at the time of infection, but a statistically significant reduction of lung bacterial load was observed even when the therapy was initiated once the infection had already been established. The protection involving enhanced phagocytosis and then neutrophil mediated killing of infected cells was IgA isotype mediated, because treatment with an IgG version of 2E9 antibody was not effective in human IgG receptor CD64 transgenic mice. The Acr antigen specificity of IgA antibodies for protection in humans has been indicated by their elevated serum levels in latent tuberculosis unlike the lack of IgA antibodies against the virulence-associated MPT64 antigen. Our results represent the first evidence for potential translation of mucosal immunotherapy for the management of MDR-TB.
Bacillus subtilisandEnterococcus faeciumco-fermented feed regulates lactating sow's performance, immune status and gut microbiota
MICROBIAL BIOTECHNOLOGY
Authors: Wang, Cheng; Wei, Siyu; Xu, Bocheng; Hao, Lihong; Su, Weifa; Jin, Mingliang; Wang, Yizhen
Abstract
Fermented feed (FF) is widely applied to improve swine performance. However, the understandings of the effects of FF on the immune status and gut microbiota of lactating sows and whether probiotics are the effective composition of FF are still limited. The present study aimed to investigate the performance, immune status and gut microbiota of lactating sows fed with a basal diet supplemented withBacillus subtilisandEnterococcus faeciumco-fermented feed (FF), with the probiotic combination (PRO) ofB. subtilisandE. faeciumand control diet (CON) as controls. Compared with the CON group, FF group remarkably improved the average daily feed intake of sows and the weight gain of piglets, while significantly decreased the backfat loss, constipation rate of sows and diarrhoea incidence of piglets. The yield and quality of milk of sows in FF group were improved. Besides, faecal acetate and butyrate were promoted in FF group. Additionally, FF increased the level of IgG, IgM and IL-10 and decreased the concentration of TNF-alpha in serum. Furthermore, FF reduced the abundance ofEnterobacteriaceaeand increased the level ofLactobacillusandSucciniclasticum, which were remarkably associated with growth performance and serum immune parameters. Accordingly, microbial metabolic functions including DNA repair and recombination proteins, glycolysis and gluconeogenesis, mismatch repair andd-alanine metabolism were significantly upregulated, while amino acid metabolism was downregulated in FF group. Overall, the beneficial effects of FF were superior to PRO treatment. Altogether, administration of FF during lactation improved the performance and immune status, and modulated gut microbiota of sows. Probiotics are not the only one effective compound of FF.