Innate Immune Homeostasis by the Homeobox Gene Caudal and Commensal-Gut Mutualism in Drosophila

By Ji-Hwan Ryu, Sung‐Hee Kim, H. Lee, J. Bai, Y. Nam, Jin-Woo Bae, Dong Gun Lee, Seung Chul Shin, Eun-Mi Ha, W. Lee. Science, 2008

837 citations recorded by the source corpus.

Although commensalism with gut microbiota exists in all metazoans, the host factors that maintain this homeostatic relationship remain largely unknown. We show that the intestinal homeobox gene Caudal regulates the commensal-gut mutualism by repressing nuclear factor kappa B–dependent antimicrobial peptide genes. Inhibition of Caudal expression in flies via RNA interference led to overexpression of antimicrobial peptides, which in turn altered the commensal population within the intestine. In particular, the dominance of one gut microbe, Gluconobacter sp. strain EW707, eventually led to gut cell apoptosis and host mortality. However, restoration of a healthy microbiota community and normal host survival in the Caudal-RNAi flies was achieved by reintroduction of the Caudal gene. These results reveal that a specific genetic deficiency within a host can profoundly influence the gut commensal microbial community and host physiology.

Subfields: Genetics, Immunology, Insect Science

View Paper: https://www.semanticscholar.org/paper/3da45ec3e4dd22e5682e6f2166763a520913ae3e

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Immunology

In Insect Science

Citations in the corpus

Acetic Acid Bacteria (2016, background): “melanogaster and described as involved in the host’s immune homeostasis (Ryu et al. 2008; Roh et al. 2008). Although a constant microbial core could not be determined, the aforementioned families were hosted by many fly species, independently from the host’s taxonomic, ecological, or geographic char”
Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut (2008, background): “Dysregulation of nuclear factor-κB (NF-κB)-dependent expression of antimicrobial peptides in the intestinal epithelium of Drosophila melanogaster resulted in the outgrowth of one 'pathogenic' commensal community, which led to the death of the hos”
Animals in a bacterial world, a new imperative for the life sciences (2013, background): “Intriguingly, the host regulatory pathways that control immune responses to microbes appear also to have central roles in animal development, underscoring the intimate relationships between development and host-microbe interactions (58, 59).”
Gut microbiome dysbiosis and honeybee health (2011, background): “Ryu et al. (2008) discovered a mutualistic relationship between the endogenous gut microbiome and the immune system of the Drosophila fruit fly, revealing that the fly’s normal microbiome has a major role in controlling the growth of pathogenic bacteria.”
The gut microbiota of insects - diversity in structure and function. (2013, background): “In Caudaldeficient flies, a constitutive AMP production occurs and causes shifts in the gut microbiota and the disintegration of the epithelial cell layer (Ryu et al., 2008).”
Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut (2009, background): “In the case of infection, we expected the critical inputs to be the Toll and/or IMD innate immunity pathways, which signal via NF-kB transcription factors (Ryu et al., 2008).”
Bacterial Communities of Diverse Drosophila Species: Ecological Context of a Host–Microbe Model System (2011, background): “The putative commensal bacterial genera studied by Ryu et al., 2008 are members of the family Acetobacteraceae (Acetobacter, Glucoacetobacter, Commensalibacter) and the genus Lactobacillus (L. plantarum and L. brevis).”
The lactic acid bacteria involved in the production of bee pollen and bee bread (2009, background): “The microflora of insects is much less complex than in humans, but Ryu et al. (2008) have shown that in the fruit fly Drosophila, a mutualistic relationship between the endogenous gut flora and their host was discovered.”
Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation. (2009, background): “Recent studies in Drosophila have revealed that multiple levels of regulation are employed to limit Imd pathway activity in the gut and prevent excessive or prolonged immune activation (Lhocine et al., 2008; Maillet et al., 2008; Ryu et al., 2008).”
Lactobacillus plantarum promotes Drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing. (2011, background): “…promotes immunomodulation by triggering the expression of negative regulators of innate immune signaling in intestinal epithelial cells (Lhocine et al., 2008; Ryu et al., 2008) and influences epithelial homeostasis through the promotion of intestinal stem cell activity (Buchon et al., 2009).”
Outdoor immunology: methodological considerations for ecologists (2011, background): “Mechanisms to explain these complex interactions between parasites, the host’s microbial flora and immune system are not yet fully understood (but see RakoffNahoum et al. 2004; Ryu et al. 2008; Rodrigues et al. 2010).”