Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 42; pp. 17378 - 17383
• Main Authors: Limmer, Stefanie, Haller, Samantha, Drenkard, Eliana, Lee, Janice, Yu, Shen, Kocks, Christine, Ausubel, Frederick M, Ferrandon, Dominique
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.10.2011; National Acad Sciences
• Subjects: Administration, Oral; Animals; Animals, Genetically Modified; Bacteremia; Bacteremia - immunology; Bacteria; Bacterial infections; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Biological Sciences; Cell mediated immunity; Disease Models, Animal; Drosophila; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila melanogaster - immunology; Drosophila melanogaster - microbiology; Epithelium; Genes, Insect; Genes, Viral; Gram-negative bacteria; Hemocoel; Hemocytes; Hemolymph; Hemolymph - microbiology; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - immunology; Immune response; Immunity, Cellular; Immunology; immunosuppression (physiological); Infections; Insects; intestinal mucosa; Intestine; mutants; Mutation; neutralization; Oral infection; Pathogenesis; Pathogens; Pathology; Proteinase; proteinases; Pseudomonas aeruginosa; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - immunology; Pseudomonas aeruginosa - pathogenicity; Pseudomonas Infections - immunology; quorum sensing; Quorum Sensing - immunology; RhlR protein; Tolls; Trans-Activators - genetics; Trans-Activators - immunology; Transcription factors; Type III secretion system; Virulence; Virulence - immunology; virulence factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1114907108

An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host–pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated.