Joint Observation of the Galactic Center with MAGIC and CTA-LST-1

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations

Effects of Mycobacteria Major Secretion Protein, Ag85B, on Allergic Inflammation in the Lung

<div><p>Many epidemiological studies have suggested that the recent increase in prevalence and severity of allergic diseases such as asthma is inversely correlated with <i>Mycobacterium bovis</i> bacillus Calmette Guerin (BCG) vaccination. However, the underlying mechanisms by which mycobacterial components suppress allergic diseases are not yet fully understood. Here we showed the inhibitory mechanisms for development of allergic airway inflammation by using highly purified recombinant Ag85B (rAg85B), which is one of the major protein antigens secreted from <i>M. tuberculosis</i>. Ag85B is thought to be a single immunogenic protein that can elicit a strong Th1-type immune response in hosts infected with mycobacteria, including individuals vaccinated with BCG. Administration of rAg85B showed a strong inhibitory effect on the development of allergic airway inflammation with induction of Th1-response and IL-17and IL-22 production. Both cytokines induced by rAg85B were involved in the induction of Th17-related cytokine-production innate immune cells in the lung. Administration of neutralizing antibodies to IL-17 or IL-22 in rAg85B-treated mice revealed that IL-17 induced the infiltration of neutrophils in BAL fluid and that allergen-induced bronchial eosinophilia was inhibited by IL-22. Furthermore, enhancement of the expression of genes associated with tissue homeostasis and wound healing was observed in bronchial tissues after rAg85B administration in a Th17-related cytokine dependent manner. The results of this study provide evidence for the potential usefulness of rAg85B as a novel approach for anti-allergic effect and tissue repair other than the role as a conventional TB vaccine.</p></div

Innate immune cells that secrete Th17-related cytokines are induced by rAg85B administration in BAL fluid.

<p>OVA-immunized (i.p., day0 and 14) and sensitized (5% aerosolized-OVA, day21 to 25) BALB/c mice were challenged with PBS or rAg85B protein (i.p. (100 µg; days 0 and 14) and i.n. (20 µg; days 21, 23, and 25)). At 24 h after the last OVA sensitization, BAL fluid from naïve or OVA sensitized BALB/c mice treated with PBS or rAg85B, were harvested. BAL cells were stimulated with ionomycin and PMA for 5 h, and with brefeldin A added in the last 3 h. Flow cytometry of BAL cells from PBS-treated (upper) and rAg85B protein-treated (lower) OVA-sensitized mice stained with anti-CD3, anti-CD4, anti-CD8, anti-Gr-1, anti-γδ TCR, anti-NKp46, anti-CD11c, anti-CD127 (IL-7R) and Lineage specific marker (CD3, CD19, Gr-1, CD11b, CD11c). Numbers in quadrants indicate percent of cells in each (<i>A</i>). Intracellular IL-17 and IL-22 staining in indicated cells by flow cytometry (dot plots) and absolute numbers of those cell populations (side graphs) in the BAL fluid (<i>B, C, D, E, F, G</i>). Data are representative of at least two independent experiments (**P<0.01 compared with OVA control. error bars, s.d.; n = 6 mice).</p

Functions of rAg85B in allergic inflammation.

<p>Experimental design used to investigate the effects of rAg85B on OVA-induced allergic lung inflammation (<i>A</i>). BALB/c mice were intraperitoneally immunized with OVA on days 0 and 14. On days 21 to 25 after the first immunization, mice were exposed to aerosolized 5% OVA for 20 min. Three hours prior to OVA inhalation, the mice were i.p. (100 µg; days 0 and 14) and i.n. (20 µg; days 21, 23, and 25) administered rAg85B. One day after the last challenge, the BAL cells were counted (<i>B</i>) and OVA-specific serum IgE concentrations were determined by ELISA (<i>C</i>). Flow cytometry of BAL cells from naïve or OVA sensitized BALB/c mice treated with PBS or rAg85B, stained with anti-Gr-1 and anti-Siglec-F. Numbers adjacent to outlined area indicate percent of eosinophils (Gr-1^dull, Siglec-F⁺), and neutrophils (Gr-1⁺, Siglec-F^neg) (<i>D</i>). Formalin-fixed tissue sections were stained with hematoxylin and eosin to visualized cell recruitment (upper row, scale bar, 100 mm), Masson's trichrome (center row, scale bar, 100 mm), and α-smooth muscle actin (lower row, scale bar, 50 mm). Numbers in quadrants indicate the score scale from 0 to 5 in each. (<i>E</i>). Data are representative of at least three independent experiments. (*P<0.05, **P<0.01 compared with OVA control. error bars, s.d.; n = 6 mice).</p