Although leprosy(Hansen's disease) is one ofthe oldestknown diseases, the pathogenicity of Mycobacterium leprae (M. leprae) remains enigmatic. Indeed, the cellwall components responsible for the... Show moreAlthough leprosy(Hansen's disease) is one ofthe oldestknown diseases, the pathogenicity of Mycobacterium leprae (M. leprae) remains enigmatic. Indeed, the cellwall components responsible for the immune response against M. leprae are as yet largely unidentified. We reveal herephenolic glycolipid-III (PGL-III) as an M. leprae-specific ligand for the immune receptor Mincle. PGL-III is a scarcelypresent trisaccharide intermediate in the biosynthetic pathway toPGL-I, an abundant and characteristic M. leprae glycolipid.Using activity-based purification, we identified PGL-III as a Mincleligand that is more potent than the well-known M. tuberculosis trehalose dimycolate. The cocrystal structure of Mincle and a syntheticPGL-III analogue revealed a unique recognition mode, implying thatit can engage multiple Mincle molecules. In Mincle-deficient miceinfected with M. leprae, increased bacterial burdenwith gross pathologies were observed. These results show that PGL-IIIis a noncanonical ligand recognized by Mincle, triggering protectiveimmunity.PGL-III, a potent immunostimulatory glycolipid,is limitedin M. leprae by the quick addition of a single methylgroup to convert it into immunosuppressive PGL-I, which confers immuneescape. Show less
Goto, M.; Bailey, J.D.; Hocuk, S.; Caselli, P.; Esplugues, G.B.; Cazaux, S.M.; Spaans, M. 2018
We present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets... Show moreWe present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets and Disks with Subaru, and 1.1 {$μ$}m Hubble Space Telescope/NICMOS data. While submillimeter studies suggested there is a dust-depleted cavity with r = 0.''35, we find scattered light as close as 0.''1 (20-28 AU) from the star, with no visible cavity at H, K', or K$_s$ . We find two small-scaled spiral structures that asymmetrically shadow the outer disk. We model one of the spirals using spiral density wave theory, and derive a disk aspect ratio of h ~{} 0.18, indicating a dynamically warm disk. If the spiral pattern is excited by a perturber, we estimate its mass to be 5$^{+3}$ $_{- 4}$ M$_J$ , in the range where planet filtration models predict accretion continuing onto the star. Using a combination of non-redundant aperture masking data at L' and angular differential imaging with Locally Optimized Combination of Images at K' and K$_s$ , we exclude stellar or massive brown dwarf companions within 300 mas of the Herbig Ae star, and all but planetary mass companions exterior to 0.''5. We reach 5{$σ$} contrasts limiting companions to planetary masses, 3-4 M$_J$ at 1.''0 and 2 M$_J$ at 1.''55, using the COND models. Collectively, these data strengthen the case for MWC 758 already being a young planetary system. Show less
Grady, C.; Muto, T.; Hashimoto, J.; Fukagawa, M.; Currie, T.; Biller, B.; ... ; Tamura, M. 2013
We present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets and... Show moreWe present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets and Disks with Subaru, and 1.1 {$μ$}m Hubble Space Telescope/NICMOS data. While submillimeter studies suggested there is a dust-depleted cavity with r = 0.''35, we find scattered light as close as 0.''1 (20-28 AU) from the star, with no visible cavity at H, K', or K$_s$ . We find two small-scaled spiral structures that asymmetrically shadow the outer disk. We model one of the spirals using spiral density wave theory, and derive a disk aspect ratio of h ~{} 0.18, indicating a dynamically warm disk. If the spiral pattern is excited by a perturber, we estimate its mass to be 5$^{+3}$ $_{- 4}$ M$_J$ , in the range where planet filtration models predict accretion continuing onto the star. Using a combination of non-redundant aperture masking data at L' and angular differential imaging with Locally Optimized Combination of Images at K' and K$_s$ , we exclude stellar or massive brown dwarf companions within 300 mas of the Herbig Ae star, and all but planetary mass companions exterior to 0.''5. We reach 5{$σ$} contrasts limiting companions to planetary masses, 3-4 M$_J$ at 1.''0 and 2 M$_J$ at 1.''55, using the COND models. Collectively, these data strengthen the case for MWC 758 already being a young planetary system. Show less