IL-4i1 Regulation of Immune Protection During Mycobacterium tuberculosis Infection.

BACKGROUND: Interleukin 4 (IL-4i1)-induced gene 1 encodes L-phenylalanine oxidase that catabolizes phenylalanine into phenylpyruvate. IL-4i1 is mainly expressed by antigen-presenting cells (APCs), inhibits T-cell proliferation, regulates B-cell activation, modulates T cell responses, and drives macrophage polarization, but its role in bacterial infections is understudied. METHODS: We evaluated IL-4i1 deletion in macrophages and mice on infection with virulent H37Rv and W-Beijing lineage hypervirulent HN878 Mycobacterium tuberculosis (Mtb) strains. The bacterial growth and proinflammatory responses were measured in vitro and in vivo. Histopathological analysis, lung immune cell recruitment, and macrophage activation were assessed at the early and chronic stages of Mtb infection. RESULTS: IL-4i1-deficient (IL-4i1-/-) mice displayed increased protection against acute H37Rv, HN878 and chronic HN878 Mt infections, with reduced lung bacterial burdens and altered APC responses compared with wild-type mice. Moreover, "M1-like" interstitial macrophage numbers, and nitrite and Interferon-γ production were significantly increased in IL-4i1-/- mice compared with wild-type mice during acute Mtb HN878 infection. CONCLUSIONS: Together, these data suggest that IL-4i1 regulates APC-mediated inflammatory responses during acute and chronic Mtb infection. Hence, IL-4i1 targeting has potential as an immunomodulatory target for host-directed therapy.

Child and adolescent mental health services and systems in low and middle-income countries: from mapping to strengthening.

PURPOSE OF REVIEW: Most of the world's children and adolescents live in low and middle-income countries (LMICs) where mental health services are very limited. Here, we reviewed literature over the last 18 months describing the current landscape of child and adolescent mental health services and systems (CAMHSS) in LMICs, and present findings from systems strengthening research. RECENT FINDINGS: The challenges in CAMHSS are well described with little change over the last two decades. Fortunately, research has started to move from 'mapping' towards systems 'strengthening'. Using the WHO Assessment Instrument for Mental Health Systems (WHO-AIMS) framework, we reviewed recent CAMHSS innovations. Clinical care and human resource innovations focused on primary care with validation of screening tools, training and task-sharing for capacity-building. Intersectoral collaboration emerged as a priority domain for strengthening, alongside a theme around the importance of participatory research to inform policy reforms. The potential role of digital technology to strengthen CAMHSS was identified as an emerging theme. SUMMARY: There is an urgent need to increase the priority of CAMHSS in LMICs. This will require innovations at multiple levels aimed at all CAMHSS domains, with active participation of all relevant local stakeholders to ensure the translation of research into policy and practice.