Models of infectious diseases in the fruit fly <i>Drosophila melanogaster</i>

Dionne, Marc S.; Schneider, David

doi:10.1242/dmm.000307

Cited by 93 publications

(79 citation statements)

References 51 publications

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“…Owing to their tremendous experimental tractability and wealth of genetic tools, Drosophila are a powerful model to explore innate immunity and microbial pathogenesis (Dionne and Schneider 2008;O'Callaghan and Vergunst 2010). Scientists first discovered Toll receptors while studying Drosophila embryogenesis almost 30 years ago (Anderson et al 1985), and it is now apparent that tolllike receptors (TLRs) function as critical innate immune sensors in evolutionarily diverse organisms, including humans.…”

Section: Fruit Flymentioning

confidence: 99%

Exploring host–microbiota interactions in animal models and humans

2013

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The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host-microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host-microbiota interactions and explore recent human microbiome studies.The distinctive body plans of animals offer many niches for members of the archaeal and bacterial kingdoms. While the lumen of the human distal gut is one of the most densely populated ecosystems on our planet, humans and other animals harbor several microbiomes on and within their body surfaces such as the respiratory and urogenital tracts and the skin. As the gut has evolved from the relatively simple tube of the ancient cyclostomatida to the more highly compartmentalized gastrointestinal tracts of mammalian species, the diversity and complexity of the microbial inhabitants of those spaces has increased as well (Fig.

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Section: Fruit Flymentioning

confidence: 99%

Exploring host–microbiota interactions in animal models and humans

2013

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“…The fruit fly D. melanogaster is a powerful, genetically malleable model for studying host-pathogen interactions and innate immunity (26)(27)(28)(29), bolstered by the fact that nearly 75% of human genes implicated in disease have a functional homolog in flies (30). Secretion of antimicrobial peptides (AMPs), melanization, and the phagocytic activity of hemocytes are the primary innate immune mechanisms that the flies use to combat infection (27,31).…”

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confidence: 99%

Host and Bacterial Factors Control Susceptibility of Drosophila melanogaster to Coxiella burnetii Infection

et al. 2017

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Coxiella burnetii is the causative agent of Q fever, a zoonotic disease that threatens both human and animal health. Due to the paucity of experimental animal models, little is known about how host factors interface with bacterial components and affect pathogenesis. Here, we used Drosophila melanogaster, in conjunction with the biosafety level 2 (BSL2) Nine Mile phase II (NMII) clone 4 strain of C. burnetii, as a model to investigate host and bacterial components implicated in infection. We demonstrate that adult Drosophila flies are susceptible to C. burnetii NMII infection and that this bacterial strain, which activates the immune deficiency (IMD) pathway, is able to replicate and cause mortality in the animals. We show that in the absence of Eiger, the only known tumor necrosis factor (TNF) superfamily homolog in Drosophila, Coxiella-infected flies exhibit reduced mortality from infection. We also demonstrate that the Coxiella type 4 secretion system (T4SS) is critical for the formation of the Coxiella-containing vacuole and establishment of infection in Drosophila. Altogether, our data reveal that the Drosophila TNF homolog Eiger and the Coxiella T4SS are implicated in the pathogenesis of C. burnetii in flies. The Drosophila/NMII model mimics relevant aspects of the infection in mammals, such as a critical role of host TNF and the bacterial T4SS in pathogenesis. Our work also demonstrates the usefulness of this BSL2 model to investigate both host and Coxiella components implicated in infection.KEYWORDS Q fever, innate immunity, IMD, TNF, Eiger, NMII, pathogenesis, T4SS, tumor necrosis factor C oxiella burnetii is an obligate intracellular Gram-negative bacterium and the causative agent of the zoonosis Q fever (1). Acute C. burnetii infection in humans is characterized primarily by influenza-like symptoms and pneumonia. Domestic ruminants act as reservoir hosts of C. burnetii and have been implicated in several outbreaks of Q fever worldwide (1-3). Based on morbidity, low infectious dose, and the environmental stability of the organism, the U.S. Centers for Disease Control and Prevention (CDC) has designated C. burnetii a category B biological weapon agent (4). C. burnetii presents two antigenic forms: a pathogenic phase I variant and an attenuated phase II variant that has a truncated O chain in its lipopolysaccharide (5, 6). C. burnetii phase I is associated with Q fever, whereas phase II does not cause disease in immunocompetent hosts (7-9). The Nine Mile phase II (NMII) clone 4/RSA439 is an attenuated strain of C. burnetii derived from the virulent Nine Mile phase I (NMI) strain through repeated passages in embryonated eggs (5). Although attenuated in immunocompetent hosts, the NMII strain has been shown to be virulent to SCID mice (10) and to cause fever in gamma interferon knockout (IFN-␥ Ϫ/Ϫ ) and Toll-like receptor 2 knockout (TLR2 Ϫ/Ϫ ) mice (11). Because C. burnetii NMI and NMII strains present similar replication kinetics in tissue culture models, the NMII strain has been used as a safer o...

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“…The Drosophila immune system is well studied, which allows us to probe the relationship between injury and infection using characterized immune system mutants and previously described pathogens (13)(14)(15)(16). Insect antibacterial immunity can be broken down into three main components: production of extracellularly secreted antimicrobial peptides (AMPs), cellular phagocytosis, and melanization.…”

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confidence: 99%

Thorax Injury Lowers Resistance to Infection in Drosophila melanogaster

et al. 2014

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The route of infection can profoundly affect both the progression and outcome of disease. We investigated differences in Drosophila melanogaster defense against infection after bacterial inoculation into two sites-the abdomen and the thorax. Thorax inoculation results in increased bacterial proliferation and causes high mortality within the first few days of infection. In contrast, abdomen inoculation results in minimal mortality and lower bacterial loads than thorax inoculation. Inoculation into either site causes systemic infection. Differences in mortality and bacterial load are due to injury of the thorax and can be recapitulated by abdominal inoculation coupled with aseptic wounding of the thorax. This altered resistance appears to be independent of classical immune pathways and opens new avenues of research on the role of injury during defense against infection.

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Models of infectious diseases in the fruit fly Drosophila melanogaster

Cited by 93 publications

References 51 publications

Exploring host–microbiota interactions in animal models and humans

Exploring host–microbiota interactions in animal models and humans

Host and Bacterial Factors Control Susceptibility of Drosophila melanogaster to Coxiella burnetii Infection

Thorax Injury Lowers Resistance to Infection in Drosophila melanogaster

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