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Granulomas are organized host immune structures composed of tightly interposed macrophages and other cells that form in response to a variety of persistent stimuli, both infectious and noninfectious. The tuberculous granuloma is essential for host containment of mycobacterial infection, although it does not always eradicate it. Therefore, it is considered a host-beneficial, if incompletely efficacious, immune response. The Mycobacterium RD1 locus encodes a specialized secretion system that promotes mycobacterial virulence by an unknown mechanism. Using transparent zebrafish embryos to monitor the infection process in real time, we found that RD1-deficient bacteria fail to elicit efficient granuloma formation despite their ability to grow inside of infected macrophages. We showed that macrophages infected with virulent mycobacteria produce an RD1-dependent signal that directs macrophages to aggregate into granulomas. This Mycobacterium-induced macrophage aggregation in turn is tightly linked to intercellular bacterial dissemination and increased bacterial numbers. Thus, mycobacteria co-opt host granulomas for their virulence.

Tuberculosis is caused by mycobacteria, intracellular pathogens that infect host macrophages and can persist within their hosts indefinitely within immunological structures called granulomas. The outcomes of mycobacterial infection are varied and influenced by the complex steps of pathogenesis. Macrophages are recruited to the site of infection, phagocytose infecting bacteria and return to the tissues where they aggregate with other cells to form granulomas. Multiple host and bacterial factors are involved in these steps, and the role played by them has been difficult to determine in traditional animal models of tuberculosis such as the mouse. This work describes the development of a Mycobacterium marinum-zebra fish embryo model of mycobacterial disease and illustrates its use to dissect the interaction between mycobacterium and host. Zebrafish embryos are optically transparent and genetically tractable, allowing for modulation of host immune determinants and monitoring the consequences thereof in whole animals in real time. This model was used to demonstrate that innate immune components are sufficient to support all early stages of mycobacterial pathogenesis, including early granuloma formation. Step-wise dissection of pathogenesis served to challenge three central dogmas in tuberculosis. First, it showed that macrophages exert a bactericidal effect in the sole context of innate immunity, countering the prevailing idea that macrophages are safe-havens for the bacteria until adaptive immunity is invoked. Rather, we found a more complex role for macrophages: they are required to disseminate infection by transporting bacteria into tissues, even while restricting bacterial growth. Second, it was found that bacteria promote macrophage aggregation into granulomas, a paradoxical result given that they are considered key host beneficial structures. This work showed that granulomas are co-opted by the bacteria for intercellular spread. Finally, the host inflammatory cytokine Tumor Necrosis Factor was shown to be required for early macrophage restriction of mycobacterial growth. Contrary to prevailing theories, loss of TNF signaling did not prevent macrophage aggregation, but rather led to increased macrophage death rendering the bacteria extracellular and thus creating a favorable niche for their growth. In summary, this work has dissected a number of complex interactions between host and pathogen that determine infection outcomes.

Coming off a huge three week interchurch celebration in March of Dr. Margaret Pleasant Douroux's retirement from 64 years of local + churchs ministry, the internationally acclaimed author, educator, and Gospel songwriter is pulling out all the stops for her 30th Annual Heritage Music Foundation National Gospel Music Conference, June 24 to 27 in Los Angeles.

Top artists such as Nikki Giovanni, the Mighty Clouds of Joy, Tammi Bakker, Pastor Shirley Caesar, James Cleveland's Gospel Music Workshop of America Mass Choir, and the Rev. Clay Evans have recorded her songs.

Guests include the L.A. chapter of the Gospel Music Workshop of America led by Dr. Rodena Preston and directed by Herman Jones and Santa Ana's Second Baptist Church choir directed by Dwayne Roberts.

Dr. Margaret Pleasant Douroux, internationally acclaimed author, educator, and the composer of such gospel classics as 'We're Blessed,' 'Rivers of Joy,' 'He Decided,' and 'If It Had Not Been For The Lord On My Side,' hosts one of L.A.'s annual cultural treasures, the 29th Heritage Music Foundation (HMF) Gospel Music Conference and Expo.

Dr Margaret Pleasant Douroux. internationally acclaimed author, educator, and composer of such classics as We're Blessed' and If It Had Not Been For The Lord On My Side.\" hosts the 28th Annual Heritage Music Foundation Gospel Music Conference and Expo on June 26-29 in Los Angeles.

To bring back growth, the industry needs to get behind personality radio wherever it is programming new music. Satellite radio is in the same position that FM was 35 years ago. When satellite radio provides personality-based programming that can break new artists, the industry should step up to the plate with support for promotions and contests that underwrite and promote the medium. When opportunities to advertise emerge, these should be supported as well.