Host-Detrimental Role of Esx-1-Mediated Inflammasome Activation in Mycobacterial Infection

The Esx-1 (type VII) secretion system is a major virulence determinant of pathogenic mycobacteria, including Mycobacterium marinum. However, the molecular events and host-pathogen interactions underlying Esx-1-mediated virulence in vivo remain unclear. Here we address this problem in a non-lethal mouse model of M. marinum infection that allows detailed quantitative analysis of disease progression. M. marinum established local infection in mouse tails, with Esx-1-dependent formation of caseating granulomas similar to those formed in human tuberculosis, and bone deterioration reminiscent of skeletal tuberculosis. Analysis of tails infected with wild type or Esx-1-deficient bacteria showed that Esx-1 enhanced generation of proinflammatory cytokines, including the secreted form of IL-1β, suggesting that Esx-1 promotes inflammasome activation in vivo. In vitro experiments indicated that Esx-1-dependent inflammasome activation required the host NLRP3 and ASC proteins. Infection of wild type and ASC-deficient mice demonstrated that Esx-1-dependent inflammasome activation exacerbated disease without restricting bacterial growth, indicating a host-detrimental role of this inflammatory pathway in mycobacterial infection. These findings define an immunoregulatory role for Esx-1 in a specific host-pathogen interaction in vivo, and indicate that the Esx-1 secretion system promotes disease and inflammation through its ability to activate the inflammasome

(Designing for) learning computational STEM and arts integration in culturally sustaining learning ecologies

Purpose: The purpose of this paper is to explore the designed cultural ecology of a hip-hop and computational science, technology, engineering, and mathematics (STEM) camp and the ways in which that ecology contributed to culturally sustaining learning experiences for middle school youth. In using the principles of hip-hop as a CSP for design, the authors question how and what practices were supported or emerged and how they became resources for youth engagement in the space. Design/methodology/approach: The overall methodology was design research. Through interpretive analysis, it uses an example of four Black girls participating in the camp as they build a computer-controlled DJ battle station. Findings: Through a close examination of youth interactions in the designed environment – looking at their communication, spatial arrangements, choices and uses of materials and tools during collaborative project work – the authors show how a learning ecology, designed based on hip-hop and computational practices and shaped by the history and practices of the dance center where the program was held, provided access to ideational, relational, spatial and material resources that became relevant to learning through computational making. The authors also show how youth engagement in the hip-hop computational making learning ecology allowed practices to emerge that led to expansive learning experiences that redefine what it means to engage in computing. Research limitations/implications: Implications include how such ecologies might arrange relations of ideas, tools, materials, space and people to support learning and positive identity development. Originality/value: Supporting culturally sustaining computational STEM pedagogies, the article argues two original points in informal youth learning 1) an expanded definition of computing based on making grammars and the cultural practices of hip-hop, and 2) attention to cultural ecologies in designing and understanding computational STEM learning environments