Photosensitivity in epilepsy is common and has high heritability, but its genetic basis remains uncertain. Galizia et al. reveal an overrepresentation of unique variants of CHD2 — which encodes the transcriptional regulator ‘chromodomain helicase DNA-binding protein 2’ — in photosensitive epilepsies, and show that chd2 knockdown in zebrafish causes photosensitivity.

BackgroundBuruli Ulcer (BU) is a neglected, necrotizing skin disease caused by Mycobacterium ulcerans. Currently, there is no vaccine against M. ulcerans infection. Although the World Health Organization recommends a combination of rifampicin and streptomycin for the treatment of BU, clinical management of advanced stages is still based on the surgical resection of infected skin. The use of bacteriophages for the control of bacterial infections has been considered as an alternative or to be used in association with antibiotherapy. Additionally, the mycobacteriophage D29 has previously been shown to display lytic activity against M. ulcerans isolates.Methodology/Principal findingsWe used the mouse footpad model of M. ulcerans infection to evaluate the therapeutic efficacy of treatment with mycobacteriophage D29. Analyses of macroscopic lesions, bacterial burdens, histology and cytokine production were performed in both M. ulcerans-infected footpads and draining lymph nodes (DLN). We have demonstrated that a single subcutaneous injection of the mycobacteriophage D29, administered 33 days after bacterial challenge, was sufficient to decrease pathology and to prevent ulceration. This protection resulted in a significant reduction of M. ulcerans numbers accompanied by an increase of cytokine levels (including IFN-γ), both in footpads and DLN. Additionally, mycobacteriophage D29 treatment induced a cellular infiltrate of a lymphocytic/macrophagic profile.Conclusions/SignificanceOur observations demonstrate the potential of phage therapy against M. ulcerans infection, paving the way for future studies aiming at the development of novel phage-related therapeutic approaches against BU.

No abstract

Buruli ulcer is a neglected infectious disease caused byBuruli ulcer (BU) is an emerging neglected tropical disease caused by Mycobacterium ulcerans and is characterized by nonulcerative lesions that can evolve into severe ulcers (41,70).Infection by M. ulcerans poses a unique challenge for the host immune system due to the secretion of the highly cytotoxic lipidic exotoxin mycolactone (17). Mycolactone has been suggested to suppress the development of local and systemic immune responses by inhibiting cytokine production during active BU (19-21, 42, 72, 75) and compromising T-cell priming by suppressing dendritic cell function (11). However, there are no studies on the association of BU with opportunistic infections, suggesting that the immunosuppressive effects of mycolactone might not be systemic.The observations that active BU occurs in a small proportion of exposed individuals (14, 58) and when it develops frequently heals spontaneously (69) suggest the existence of protective immunity. Although the protective mechanisms remain largely unknown, several studies support that adaptive cell-mediated immunity (CMI) is relevant for the control of M. ulcerans (reviewed in reference 53). In fact, (i) M. ulcerans has an intramacrophage growth phase (66), (ii) resistance to BU is associated with the development of T helper (Th) 1 type responses and granulomata (10,20,21,23,42,48,63,70,72), (iii) the positivity of the delayed-type hypersensitivity (DTH) burulin test increases from early to advanced phases (15, 31), (iv) the histopathology of healing BU lesions in patients submitted to antibiotic treatment is consistent with CMI (49), (v) Mycobacterium bovis BCG vaccination induces transient protection in humans and in experimental infections (16,55,60,62,68), (vi) infection with HIV increases the risk of developing BU and more aggressive multifocal forms (27, 64), and (vii) the pattern of cytokine expression in BU lesions conforms with CMI and DTH (28,38,67).Therefore, to clarify whether the M. ulcerans infectious process interferes with the development of protective immunity and whether systemic immunosuppression is induced, we monitored the host immune response in the mouse model, not only in the primary site of infection but also in the draining lymph node (DLN), where the initiation of the adaptive immunity takes place. MATERIALS AND METHODSAnimals. Eight-week-old female wild-type, nude, and Rag2-deficient mice in a BALB/c background were obtained from Charles River (Barcelona, Spain). Rag-deficient BALB/c mice transgenic for the DO11.10 ␣/␤ T-cell receptor (TCR) were from Anne O'Garra (NIMR, London, United Kingdom). The studies involving animals were approved by the review committees of ICVS and the Portuguese Governmental Agency Direcção Geral de Veterinária.Experimental infections. The different M. ulcerans strains used in the present study were selected based on their virulence for mice (35,65) and on the type of mycolactone produced (26, 32, 59). M. ulcerans 5114 is a low-virulence Mexican

No abstract