Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 319 (5864): 777-782

Copyright © 2008 by the American Association for the Advancement of Science

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

Ji-Hwan Ryu,1* Sung-Hee Kim,1* Hyo-Young Lee,1,2 Jin Young Bai,1 Young-Do Nam,3 Jin-Woo Bae,3 Dong Gun Lee,4 Seung Chul Shin,1,5 Eun-Mi Ha,1 Won-Jae Lee1{dagger}

Abstract: 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.

1 Division of Molecular Life Science, Ewha Woman's University and National Creative Research Initiative Center for Symbiosystem, Seoul 120-750, South Korea.
2 Laboratoire de BBMI, Institut Pasteur, Paris 75724, France.
3 Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea.
4 School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701, South Korea.
5 Brain Korea 21 Program, Yonsei University College of Medicine, CPO Box 8044, Seoul 120-752, South Korea.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: lwj{at}

The Drosophila Imd Signaling Pathway.
H. Myllymaki, S. Valanne, and M. Ramet (2014)
J. Immunol. 192, 3455-3462
   Abstract »    Full Text »    PDF »
A Drosophila immune response against Ras-induced overgrowth.
T. Hauling, R. Krautz, R. Markus, A. Volkenhoff, L. Kucerova, and U. Theopold (2014)
Biology Open 3, 250-260
   Abstract »    Full Text »    PDF »
Persephone/Spatzle Pathogen Sensors Mediate the Activation of Toll Receptor Signaling in Response to Endogenous Danger Signals in Apoptosis-deficient Drosophila.
M. Ming, F. Obata, E. Kuranaga, and M. Miura (2014)
J. Biol. Chem. 289, 7558-7568
   Abstract »    Full Text »    PDF »
Interspecies Interactions Determine the Impact of the Gut Microbiota on Nutrient Allocation in Drosophila melanogaster.
P. D. Newell and A. E. Douglas (2014)
Appl. Envir. Microbiol. 80, 788-796
   Abstract »    Full Text »    PDF »
Specific Dietary Carbohydrates Differentially Influence the Life Span and Fecundity of Drosophila melanogaster.
O. V. Lushchak, D. V. Gospodaryov, B. M. Rovenko, I. S. Yurkevych, N. V. Perkhulyn, and V. I. Lushchak (2014)
J Gerontol A Biol Sci Med Sci 69, 3-12
   Abstract »    Full Text »    PDF »
Draft Genome Sequence of Lactobacillus plantarum Strain WJL, a Drosophila Gut Symbiont.
E.-K. Kim, Y. M. Park, O. Y. Lee, and W.-J. Lee (2013)
Genome Announc 1, e00937-13
   Abstract »    Full Text »    PDF »
Draft Genome Sequence of Lactobacillus brevis Strain EW, a Drosophila Gut Pathobiont.
E.-K. Kim, Y. M. Park, O. Y. Lee, and W.-J. Lee (2013)
Genome Announc 1, e00938-13
   Abstract »    Full Text »    PDF »
Noninvasive Analysis of Microbiome Dynamics in the Fruit Fly Drosophila melanogaster.
C. Fink, F. Staubach, S. Kuenzel, J. F. Baines, and T. Roeder (2013)
Appl. Envir. Microbiol. 79, 6984-6988
   Abstract »    Full Text »    PDF »
Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees.
G. Di Prisco, V. Cavaliere, D. Annoscia, P. Varricchio, E. Caprio, F. Nazzi, G. Gargiulo, and F. Pennacchio (2013)
PNAS 110, 18466-18471
   Abstract »    Full Text »    PDF »
Frequent Replenishment Sustains the Beneficial Microbiome of Drosophila melanogaster.
J. E. Blum, C. N. Fischer, J. Miles, and J. Handelsman (2013)
mBio 4, e00860-13
   Abstract »    Full Text »    PDF »
Transglutaminase-Catalyzed Protein-Protein Cross-Linking Suppresses the Activity of the NF-{kappa}B-Like Transcription Factor Relish.
T. Shibata, S. Sekihara, T. Fujikawa, R. Miyaji, K. Maki, T. Ishihara, T. Koshiba, and S.-i. Kawabata (2013)
Science Signaling 6, ra61
   Abstract »    Full Text »    PDF »
Mutations in the IMD Pathway and Mustard Counter Vibrio cholerae Suppression of Intestinal Stem Cell Division in Drosophila.
Z. Wang, S. Hang, A. E. Purdy, and P. I. Watnick (2013)
mBio 4, e00337-13
   Abstract »    Full Text »    PDF »
Exploring host-microbiota interactions in animal models and humans.
A. D. Kostic, M. R. Howitt, and W. S. Garrett (2013)
Genes & Dev. 27, 701-718
   Abstract »    Full Text »    PDF »
Animals in a bacterial world, a new imperative for the life sciences.
M. McFall-Ngai, M. G. Hadfield, T. C. G. Bosch, H. V. Carey, T. Domazet-Loso, A. E. Douglas, N. Dubilier, G. Eberl, T. Fukami, S. F. Gilbert, et al. (2013)
PNAS 110, 3229-3236
   Abstract »    Full Text »    PDF »
big bang gene modulates gut immune tolerance in Drosophila.
F. Bonnay, E. Cohen-Berros, M. Hoffmann, S. Y. Kim, G. L. Boulianne, J. A. Hoffmann, N. Matt, and J.-M. Reichhart (2013)
PNAS 110, 2957-2962
   Abstract »    Full Text »    PDF »
Gut and Root Microbiota Commonalities.
S. T. Ramirez-Puebla, L. E. Servin-Garciduenas, B. Jimenez-Marin, L. M. Bolanos, M. Rosenblueth, J. Martinez, M. A. Rogel, E. Ormeno-Orrillo, and E. Martinez-Romero (2013)
Appl. Envir. Microbiol. 79, 2-9
   Abstract »    Full Text »    PDF »
Physiological and stem cell compartmentalization within the Drosophila midgut.
A. Marianes and A. C. Spradling (2013)
eLife Sci 2, e00886
   Abstract »    Full Text »    PDF »
Yeast Communities of Diverse Drosophila Species: Comparison of Two Symbiont Groups in the Same Hosts.
J. A. Chandler, J. A. Eisen, and A. Kopp (2012)
Appl. Envir. Microbiol. 78, 7327-7336
   Abstract »    Full Text »    PDF »
Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis.
J. Rynes, C. D. Donohoe, P. Frommolt, S. Brodesser, M. Jindra, and M. Uhlirova (2012)
Mol. Cell. Biol. 32, 3949-3962
   Abstract »    Full Text »    PDF »
Drosophila as a model system to unravel the layers of innate immunity to infection.
I. Kounatidis and P. Ligoxygakis (2012)
Open Bio 2, 120075
   Abstract »    Full Text »    PDF »
The Drosophila Protein Mustard Tailors the Innate Immune Response Activated by the Immune Deficiency Pathway.
Z. Wang, C. D. Berkey, and P. I. Watnick (2012)
J. Immunol. 188, 3993-4000
   Abstract »    Full Text »    PDF »
Obligate Symbionts Activate Immune System Development in the Tsetse Fly.
B. L. Weiss, M. Maltz, and S. Aksoy (2012)
J. Immunol. 188, 3395-3403
   Abstract »    Full Text »    PDF »
Genetic evidence of a redox-dependent systemic wound response via Hayan Protease-Phenoloxidase system in Drosophila.
H.-J. Nam, I.-H. Jang, H. You, K.-A. Lee, and W.-J. Lee (2012)
EMBO J. 31, 1253-1265
   Abstract »    Full Text »    PDF »
Draft Genome Sequence of Gluconobacter morbifer G707T, a Pathogenic Gut Bacterium Isolated from Drosophila melanogaster Intestine.
E.-K. Kim, S.-H. Kim, H.-J. Nam, M. K. Choi, K.-A. Lee, S.-H. Choi, Y. Y. Seo, H. You, B. Kim, and W.-J. Lee (2012)
J. Bacteriol. 194, 1245
   Abstract »    Full Text »    PDF »
Draft Genome Sequence of Commensalibacter intestini A911T, a Symbiotic Bacterium Isolated from Drosophila melanogaster Intestine.
E.-K. Kim, S.-H. Kim, H.-J. Nam, M. K. Choi, K.-A. Lee, S.-H. Choi, Y. Y. Seo, H. You, B. Kim, and W.-J. Lee (2012)
J. Bacteriol. 194, 1246
   Abstract »    Full Text »    PDF »
Drosophila Microbiome Modulates Host Developmental and Metabolic Homeostasis via Insulin Signaling.
S. C. Shin, S.-H. Kim, H. You, B. Kim, A. C. Kim, K.-A. Lee, J.-H. Yoon, J.-H. Ryu, and W.-J. Lee (2011)
Science 334, 670-674
   Abstract »    Full Text »    PDF »
Disruption of the Termite Gut Microbiota and Its Prolonged Consequences for Fitness.
R. B. Rosengaus, C. N. Zecher, K. F. Schultheis, R. M. Brucker, and S. R. Bordenstein (2011)
Appl. Envir. Microbiol. 77, 4303-4312
   Abstract »    Full Text »    PDF »
The Drosophila peptidoglycan-recognition protein LF interacts with peptidoglycan-recognition protein LC to downregulate the Imd pathway.
N. Basbous, F. Coste, P. Leone, R. Vincentelli, J. Royet, C. Kellenberger, and A. Roussel (2011)
EMBO Rep. 12, 327-333
   Abstract »    Full Text »    PDF »
Danger, Microbes, and Homeostasis.
B. P. Lazzaro and J. Rolff (2011)
Science 332, 43-44
   Abstract »    Full Text »    PDF »
Negative regulation of immune responses on the fly.
K.-Z. Lee and D. Ferrandon (2011)
EMBO J. 30, 988-990
   Abstract »    Full Text »    PDF »
Drosophila melanogaster as a model for human intestinal infection and pathology.
Y. Apidianakis and L. G. Rahme (2011)
Dis. Model. Mech. 4, 21-30
   Abstract »    Full Text »    PDF »
Molecular Evidence for Multiple Infections as Revealed by Typing of Asaia Bacterial Symbionts of Four Mosquito Species.
B. Chouaia, P. Rossi, M. Montagna, I. Ricci, E. Crotti, C. Damiani, S. Epis, I. Faye, N. Sagnon, A. Alma, et al. (2010)
Appl. Envir. Microbiol. 76, 7444-7450
   Abstract »    Full Text »    PDF »
Acetic Acid Bacteria, Newly Emerging Symbionts of Insects.
E. Crotti, A. Rizzi, B. Chouaia, I. Ricci, G. Favia, A. Alma, L. Sacchi, K. Bourtzis, M. Mandrioli, A. Cherif, et al. (2010)
Appl. Envir. Microbiol. 76, 6963-6970
   Abstract »    Full Text »    PDF »
From Structure to Function: the Ecology of Host-Associated Microbial Communities.
C. J. Robinson, B. J. M. Bohannan, and V. B. Young (2010)
Microbiol. Mol. Biol. Rev. 74, 453-476
   Abstract »    Full Text »    PDF »
The POU Transcription Factor Drifter/Ventral veinless Regulates Expression of Drosophila Immune Defense Genes.
A. Junell, H. Uvell, M. M. Davis, E. Edlundh-Rose, A. Antonsson, L. Pick, and Y. Engstrom (2010)
Mol. Cell. Biol. 30, 3672-3684
   Abstract »    Full Text »    PDF »
bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans.
K. A. Estes, T. L. Dunbar, J. R. Powell, F. M. Ausubel, and E. R. Troemel (2010)
PNAS 107, 2153-2158
   Abstract »    Full Text »    PDF »
Differential regulation of mRNA stability controls the transient expression of genes encoding Drosophila antimicrobial peptide with distinct immune response characteristics.
Y. Wei, Q. Xiao, T. Zhang, Z. Mou, J. You, and W.-J. Ma (2009)
Nucleic Acids Res. 37, 6550-6561
   Abstract »    Full Text »    PDF »
Bacterial-modulated host immunity and stem cell activation for gut homeostasis.
W.-J. Lee (2009)
Genes & Dev. 23, 2260-2265
   Abstract »    Full Text »    PDF »
Whole-genome analyses reveal genetic instability of Acetobacter pasteurianus.
Y. Azuma, A. Hosoyama, M. Matsutani, N. Furuya, H. Horikawa, T. Harada, H. Hirakawa, S. Kuhara, K. Matsushita, N. Fujita, et al. (2009)
Nucleic Acids Res. 37, 5768-5783
   Abstract »    Full Text »    PDF »
Primary immune deficiencies affecting lymphocyte differentiation: lessons from the spectrum of resulting infections.
M. C. Cook and S. G. Tangye (2009)
Int. Immunol. 21, 1003-1011
   Abstract »    Full Text »    PDF »
Infection induces a survival program and local remodeling in the airway epithelium of the fly.
C. Wagner, K. Isermann, and T. Roeder (2009)
FASEB J 23, 2045-2054
   Abstract »    Full Text »    PDF »
Acetobacter tropicalis Is a Major Symbiont of the Olive Fruit Fly (Bactrocera oleae).
I. Kounatidis, E. Crotti, P. Sapountzis, L. Sacchi, A. Rizzi, B. Chouaia, C. Bandi, A. Alma, D. Daffonchio, P. Mavragani-Tsipidou, et al. (2009)
Appl. Envir. Microbiol. 75, 3281-3288
   Abstract »    Full Text »    PDF »
AU-Rich Elements Regulate Drosophila Gene Expression.
F. Cairrao, A. S. Halees, K. S. A. Khabar, D. Morello, and N. Vanzo (2009)
Mol. Cell. Biol. 29, 2636-2643
   Abstract »    Full Text »    PDF »
Bacterial-mucosal interactions in inflammatory bowel disease--an alliance gone bad.
M. Chichlowski and L. P. Hale (2008)
Am J Physiol Gastrointest Liver Physiol 295, G1139-G1149
   Abstract »    Full Text »    PDF »
Phylogenetic Characterization of Two Novel Commensal Bacteria Involved with Innate Immune Homeostasis in Drosophila melanogaster.
S. W. Roh, Y.-D. Nam, H.-W. Chang, K.-H. Kim, M.-S. Kim, J.-H. Ryu, S.-H. Kim, W.-J. Lee, and J.-W. Bae (2008)
Appl. Envir. Microbiol. 74, 6171-6177
   Abstract »    Full Text »    PDF »
The Obligate Mutualist Wigglesworthia glossinidia Influences Reproduction, Digestion, and Immunity Processes of Its Host, the Tsetse Fly.
R. Pais, C. Lohs, Y. Wu, J. Wang, and S. Aksoy (2008)
Appl. Envir. Microbiol. 74, 5965-5974
   Abstract »    Full Text »    PDF »
Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine.
C. Zaph, Y. Du, S. A. Saenz, M. G. Nair, J. G. Perrigoue, B. C. Taylor, A. E. Troy, D. E. Kobuley, R. A. Kastelein, D. J. Cua, et al. (2008)
J. Exp. Med. 205, 2191-2198
   Abstract »    Full Text »    PDF »
Models of infectious diseases in the fruit fly Drosophila melanogaster.
M. S. Dionne and D. S. Schneider (2008)
Dis. Model. Mech. 1, 43-49
   Abstract »    Full Text »    PDF »
Bacterial-Modulated Signaling Pathways in Gut Homeostasis.
W.-J. Lee (2008)
Science Signaling 1, pe24
   Abstract »    Full Text »    PDF »
IMMUNOLOGY: The Right Resident Bugs.
N. Silverman and N. Paquette (2008)
Science 319, 734-735
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882