Wolbachia-Mediated Antibacterial Protection and Immune Gene Regulation in Drosophila

Wong, Zhee Sheen; Hedges, Lauren M.; Brownlie, Jeremy C.; Johnson, Karyn N.

doi:10.1371/journal.pone.0025430

Cited by 115 publications

(115 citation statements)

References 42 publications

(93 reference statements)

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“…We note that all D. melanogaster strains, as well as the wild-type Drosophila simulans strain, were confirmed to be infected with Wolbachia by PCR using previously described primers (28). However, Wolbachia status is unlikely to affect susceptibility to EPNs or their bacterial endosymbionts: although Wolbachia infection may protect against some viral infections (29, 30), it does not appear to protect against other types of infections and has little or no effect on AMP expression (29,(31)(32)(33).…”

Section: Methodsmentioning

confidence: 90%

Variation in the Susceptibility of Drosophila to Different Entomopathogenic Nematodes

2015

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Entomopathogenic nematodes (EPNs) in the genera Heterorhabditis and Steinernema are lethal parasites of insects that are of interest as models for understanding parasite-host interactions and as biocontrol agents for insect pests. EPNs harbor a bacterial endosymbiont in their gut that assists in insect killing. EPNs are capable of infecting and killing a wide range of insects, yet how the nematodes and their bacterial endosymbionts interact with the insect immune system is poorly understood. Here, we develop a versatile model system for understanding the insect immune response to parasitic nematode infection that consists of seven species of EPNs as model parasites and five species of Drosophila fruit flies as model hosts. We show that the EPN Steinernema carpocapsae, which is widely used for insect control, is capable of infecting and killing D. melanogaster larvae. S. carpocapsae is associated with the bacterium Xenorhabdus nematophila, and we show that X. nematophila induces expression of a subset of antimicrobial peptide genes and suppresses the melanization response to the nematode. We further show that EPNs vary in their virulence toward D. melanogaster and that Drosophila species vary in their susceptibilities to EPN infection. Differences in virulence among different EPN-host combinations result from differences in both rates of infection and rates of postinfection survival. Our results establish a powerful model system for understanding mechanisms of host-parasite interactions and the insect immune response to parasitic nematode infection. E ntomopathogenic nematodes (EPNs) of the genera Steinernema and Heterorhabditis are insect-parasitic nematodes that are phylogenetically distant but share a similar life cycle as a result of convergent evolution (1). EPNs offer numerous advantages as model parasitic nematodes, including small size, short generation time, and amenability to in vitro culturing (2). 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 (3-6). However, the insect immune response to EPN infection is poorly understood.During a particular developmental stage called the infective juvenile (IJ), EPNs infect insects (Fig. 1A). IJs are developmentally arrested, third-stage larvae analogous to the dauer stage of freeliving nematodes (7). IJs actively seek out insect hosts using chemosensory cues (8-10) and infect either by entering through natural body openings or by penetrating the insect cuticle (11). IJs harbor their bacterial endosymbiont in their gut and deposit it into the insect upon infection, where it assists the nematode in killing the insect, digesting insect tissues, and inhibiting the growth of o...

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Section: Methodsmentioning

confidence: 90%

Variation in the Susceptibility of Drosophila to Different Entomopathogenic Nematodes

2015

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“…Natural and experimental infections of Drosophila and mosquitoes with the overreplicating and lifeshortening wMelPop strain can induce up-regulation of host immune responses and inhibit microbial infection with viruses, protozoa, and helminth parasites (27)(28)(29)(30). Nevertheless, not all Wolbachia-host associations lead to activation of host immunity, and among the strains that do not activate host immunity are natural strains infecting Drosophila and Aedes aegypti (31,32). The induction of host defense and protection from microbial infection therefore is strain dependent and appears to be restricted to strains that have a high replication rate and widespread tissue tropisms (29,31,33).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, not all Wolbachia-host associations lead to activation of host immunity, and among the strains that do not activate host immunity are natural strains infecting Drosophila and Aedes aegypti (31,32). The induction of host defense and protection from microbial infection therefore is strain dependent and appears to be restricted to strains that have a high replication rate and widespread tissue tropisms (29,31,33). Alternately, it has been suggested that the metabolic demands of such overreplicating bacteria may prevent microbial infection and transmission through competition for host cell resources (27).…”

Section: Discussionmentioning

confidence: 99%

Autophagy regulates Wolbachia populations across diverse symbiotic associations

Voronin

Cook

Steven

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

110

105

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Wolbachia are widespread and abundant intracellular symbionts of arthropods and filarial nematodes. Their symbiotic relationships encompass obligate mutualism, commensalism, parasitism, and pathogenicity. A consequence of these diverse associations is that Wolbachia encounter a wide range of host cells and intracellular immune defense mechanisms of invertebrates, which they must evade to maintain their populations and spread to new hosts. Here we show that autophagy, a conserved intracellular defense mechanism and regulator of cell homeostasis, is a major immune recognition and regulatory process that determines the size of Wolbachia populations. The regulation of Wolbachia populations by autophagy occurs across all distinct symbiotic relationships and can be manipulated either chemically or genetically to modulate the Wolbachia population load. The recognition and activation of host autophagy is particularly apparent in rapidly replicating strains of Wolbachia found in somatic tissues of Drosophila and filarial nematodes. In filarial nematodes, which host a mutualistic association with Wolbachia, the use of antibiotics such as doxycycline to eliminate Wolbachia has emerged as a promising approach to their treatment and control. Here we show that the activation of host nematode autophagy reduces bacterial loads to the same magnitude as antibiotic therapy; thus we identify a bactericidal mode of action targeting Wolbachia that can be exploited for the development of chemotherapeutic agents against onchocerciasis, lymphatic filariasis, and heartworm.Brugia malayi | innate immunity | chemotherapy | helminth | endosymbiont W olbachia is a widespread and abundant endosymbiotic bacterium of arthropods and filarial nematodes that resides in vacuoles of host germline and somatic cells. Wolbachia show a diverse variety of symbiotic associations with their host, ranging from obligate mutualism in filarial nematodes to commensal, parasitic, or pathogenic associations in insects and other arthropod hosts (1-5).In filarial nematodes Wolbachia is obligatory for normal larval growth and development, embryogenesis, and survival of adult worms (1). Although the molecular basis of this mutualistic relationship remains unknown, a comparison of host and bacterial genomes suggests that intact biosynthetic pathways for haem, nucleotides, riboflavin, and FAD may be among the contributions of the bacteria to the biology of the nematode host (6-8). The biological processes most sensitive to Wolbachia loss include larval growth and development and embryogenesis in adult females. These processes have a high metabolic demand because of the rapid growth, development, and organogenesis of the nematode and are associated with the rapid expansion of Wolbachia populations following larval infection of mammalian hosts and in reproductively active adult females (9). Loss of Wolbachia results in extensive apoptosis of germline and somatic cells of embryos, microfilariae, and fourth-stage (L4) larvae, presumably because of the lack of provision of ...

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“…Notably, when the same fly combinations were challenged with mortality-inducing bacteria, including Erwinia carotovora, none of the Wolbachia strains mediated antibacterial protection (47). The difference in response between antiviral and antibacterial protection in the same fly-Wolbachia combination indicates that the Wolbachia-mediated mechanism of antiviral protection differs from the mechanism of antibacterial protection (47).…”

mentioning

confidence: 99%

“…When five D. simulans-Wolbachia combinations were screened for antiviral protection by viral challenge, three combinations were protected (CO-wAu, Me29-wMel, and DSR-wRi), whereas the other two were not (DSH-wHa and N7NO-wNo) (36). Notably, when the same fly combinations were challenged with mortality-inducing bacteria, including Erwinia carotovora, none of the Wolbachia strains mediated antibacterial protection (47). The difference in response between antiviral and antibacterial protection in the same fly-Wolbachia combination indicates that the Wolbachia-mediated mechanism of antiviral protection differs from the mechanism of antibacterial protection (47).…”

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confidence: 99%

Antiviral Protection and the Importance of Wolbachia Density and Tissue Tropism in Drosophila simulans

Osborne

Iturbe‐Ormaetxe

Brownlie

et al. 2012

Appl Environ Microbiol

Self Cite

195

193

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dWolbachia, a maternally transmitted endosymbiont of insects, is increasingly being seen as an effective biological control agent that can interfere with transmission of pathogens, including dengue virus. However, the mechanism of antiviral protection is not well understood. The density and distribution of Wolbachia in host tissues have been implicated as contributing factors by previous studies with both mosquitoes and flies. Drosophila flies infected with five diverse strains of Wolbachia were screened for the ability to mediate antiviral protection. The three protective Wolbachia strains were more closely related and occurred at a higher density within whole flies than the two nonprotective Wolbachia strains. In this study, to further investigate the relationship between whole-fly Wolbachia density and the ability to mediate antiviral protection, tetracycline was used to decrease the abundance of the high-density, protective Wolbachia strain wAu prior to viral challenge. Antiviral protection was lost when the density of the protective Wolbachia strain was decreased to an abundance similar to that of nonprotective Wolbachia strains. We determined the Wolbachia density and distribution in tissues of the same five fly-Wolbachia combinations as used previously. The Wolbachia density within the head, gut, and Malpighian tubules correlated with the ability to mediate antiviral protection. These findings may facilitate the development of Wolbachia biological control strategies and help to predict host-Wolbachia pairings that may interfere with virus-induced pathology.

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Wolbachia-Mediated Antibacterial Protection and Immune Gene Regulation in Drosophila

Cited by 115 publications

References 42 publications

Variation in the Susceptibility of Drosophila to Different Entomopathogenic Nematodes

Variation in the Susceptibility of Drosophila to Different Entomopathogenic Nematodes

Autophagy regulates Wolbachia populations across diverse symbiotic associations

Antiviral Protection and the Importance of Wolbachia Density and Tissue Tropism in Drosophila simulans

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