Nematodes, Bacteria, and Flies: A Tripartite Model for Nematode Parasitism

Abstract

More than a quarter of the world's population is infected with nematode parasites, and more than a hundred species of nematodes are parasites of humans [1-3]. Despite extensive morbidity and mortality caused by nematode parasites, the biological mechanisms of host-parasite interactions are poorly understood, largely because of the lack of genetically tractable model systems. We have demonstrated that the insect parasitic nematode Heterorhabditis bacteriophora, its bacterial symbiont Photorhabdus luminescens, and the fruit fly Drosophila melanogaster constitute a tripartite model for nematode parasitism and parasitic infection. We find that infective juveniles (IJs) of Heterorhabditis, which contain Photorhabdus in their gut, can infect and kill Drosophila larvae. We show that infection activates an immune response in Drosophila that results in the temporally dynamic expression of a subset of antimicrobial peptide (AMP) genes, and that this immune response is induced specifically by Photorhabdus. We also investigated the cellular and molecular mechanisms underlying IJ recovery, the developmental process that occurs in parasitic nematodes upon host invasion and that is necessary for successful parasitism. We find that the chemosensory neurons and signaling pathways that control dauer recovery in Caenorhabditis elegans also control IJ recovery in Heterorhabditis, suggesting conservation of these developmental processes across free-living and parasitic nematodes.

Variation in the Susceptibility of Drosophila to Different Entomopathogenic Nematodes

“…The AMP genes diptericin and drosomycin have also been shown to be upregulated following direct injection of either P. luminescens or X. nematophila into D. melanogaster adults (43). However, the AMP response of D. melanogaster to infection with S. carpocapsae symbiont IJs had not yet been examined, and the extent to which AMP expression is induced by EPNs versus their bacterial endosymbionts remains unclear (4,6,45).…”

“…Studies of a number of insects, including the cecropia moth Hyalophora cecropia, the beet armyworm Spodoptera exigua, and the tobacco hornworm Manduca sexta have shown that EPN infection can induce expression of AMP genes and that both the nematode and the bacteria can suppress AMP activity (45)(46)(47)(48)(49). We previously showed that infection of D. melanogaster larvae with H. bacteriophora symbiont IJs resulted in expression of four AMP genes, attacin, diptericin, drosomycin, and metchnikowin, and that this expression was a specific response to P. luminescens (4). Similar results were subsequently observed for infection of M. sexta with H. bacteriophora symbiont IJs, thus validating D. melanogaster as a model for other insect hosts (45).…”

“…Both the nematode and its bacterial endosymbiont appear to inhibit some aspects of AMP production, melanization, encapsulation, and phagocytosis (11,(16)(17)(18). Studies using D. melanogaster larvae as a model host for the EPN Heterorhabditis bacteriophora and its endosymbiont Photorhabdus luminescens have shown that infection induces expression of a large number of immune genes, including AMPs, and that AMP expression is primarily a response to the bacterial endosymbiont rather than to the nematode (4,19). Infection also stimulates clotting, and clotting mutants show decreased survival in response to H. bacteriophora-P. luminescens infection (20,21).…”

“…EPN infective larvae are associated with bacterial endosymbionts: Steinernema species are associated with bacteria in the genus Xenorhabdus, and Heterorhabditis species are associated with bacteria in the genus Photorhabdus (1). At least some EPNs are capable of infecting the fruit fly Drosophila melanogaster, providing a genetically tractable system for understanding the immune response to parasitic nematodes and their bacterial endosymbionts (3)(4)(5)(6). However, the insect immune response to EPN infection is poorly understood.…”

Estudo de atividades amidásicas na linhagem MN7 de Photorhabdus luminescens luminescens, isolada da linhagem LPP7 de Heterorhabditis baujardi.

“…Após a invasão, o JI perde sua cutícula externa, e regurgita as bactérias Photorhabdus, presentes em seu intestino, na hemolinfa do inseto (Figura 3B), e essas são responsáveis por efetuar a evasão do sistema imune do inseto e a patogenicidade da infecção (HALLEM et al, 2007). A perda da cutícula externa e a regurgitação das bactérias após a entrada no corpo do inseto caracterizam o processo chamado de recuperação do JI.…”