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A worm's best friend: recruitment of neutrophils by Wolbachia confounds eosinophil degranulation against the filarial nematode Onchocerca ochengi.

Hansen RD, Trees AJ, Bah GS, Hetzel U, Martin C, Bain O, Tanya VN, Makepeace BL - Proc. Biol. Sci. (2010)

Bottom Line: In this study, cattle infected with Onchocerca ochengi received adulticidal regimens of oxytetracycline or melarsomine.In contrast to oxytetracycline, melarsomine did not directly affect Wolbachia viability.Taken together, these data offer strong support for the hypothesis that Wolbachia confers longevity on O. ochengi through a defensive mutualism, which diverts a potentially lethal effector cell response.

View Article: PubMed Central - PubMed

Affiliation: Liverpool School of Tropical Medicine, School of Veterinary Science and Institute of Infection and Global Health, University of Liverpool, , Liverpool L69 7ZJ, UK.

ABSTRACT
Onchocerca ochengi, a filarial parasite of cattle, represents the closest relative of the human pathogen, Onchocerca volvulus. Both species harbour Wolbachia endosymbionts and are remarkable in that adult female worms remain viable but sessile for many years while surrounded by host cells and antibodies. The basis of the symbiosis between filariae and Wolbachia is thought to be metabolic, although a role for Wolbachia in immune evasion has received little attention. Neutrophils are attracted to Wolbachia, but following antibiotic chemotherapy they are replaced by eosinophils that degranulate on the worm cuticle. However, it is unclear whether the eosinophils are involved in parasite killing or if they are attracted secondarily to dying worms. In this study, cattle infected with Onchocerca ochengi received adulticidal regimens of oxytetracycline or melarsomine. In contrast to oxytetracycline, melarsomine did not directly affect Wolbachia viability. Eosinophil degranulation increased significantly only in the oxytetracycline group; whereas nodular gene expression of bovine neutrophilic chemokines was lowest in this group. Moreover, intense eosinophil degranulation was initially associated with worm vitality, not degeneration. Taken together, these data offer strong support for the hypothesis that Wolbachia confers longevity on O. ochengi through a defensive mutualism, which diverts a potentially lethal effector cell response.

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Related in: MedlinePlus

Ultrastructure of O. ochengi onchocercomata at 12 weeks. (a) Hypodermis of an untreated worm showing abundant Wolbachia endosymbionts (W). (b) The cuticle (C) of an untreated worm displaying normal structure, alongside an adherent neutrophil (N) surrounded by numerous extracellular granules (EG). (c) A worm section from the melarsomine (MEL) group displaying intact Wolbachia (W) beneath the hypodermal lamellae (HL) and the cuticle (C). (d) Eosinophils (E) attached to Splendore-Hoeppli deposits (SH) on the cuticle (C) of a worm from the MEL group. (e) The pseudopodium (P) of a degranulating eosinophil (DE) entering a cleft in the cuticle (C) of an oxytetracycline (OXY)-treated worm. (f) Two eosinophils (E) adjacent to the paired uteri (U) within the pseudocoelomic cavity of a worm from the OXY group; eosinophils are also visible on the host side of the cuticular (C) interface. Note the highly vacuolated hypodermis. Scale bars: (a–e) 2 µm; (f)10 µm.
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RSPB20102367F3: Ultrastructure of O. ochengi onchocercomata at 12 weeks. (a) Hypodermis of an untreated worm showing abundant Wolbachia endosymbionts (W). (b) The cuticle (C) of an untreated worm displaying normal structure, alongside an adherent neutrophil (N) surrounded by numerous extracellular granules (EG). (c) A worm section from the melarsomine (MEL) group displaying intact Wolbachia (W) beneath the hypodermal lamellae (HL) and the cuticle (C). (d) Eosinophils (E) attached to Splendore-Hoeppli deposits (SH) on the cuticle (C) of a worm from the MEL group. (e) The pseudopodium (P) of a degranulating eosinophil (DE) entering a cleft in the cuticle (C) of an oxytetracycline (OXY)-treated worm. (f) Two eosinophils (E) adjacent to the paired uteri (U) within the pseudocoelomic cavity of a worm from the OXY group; eosinophils are also visible on the host side of the cuticular (C) interface. Note the highly vacuolated hypodermis. Scale bars: (a–e) 2 µm; (f)10 µm.

Mentions: In worm sections from the CON group at 12 wpt, Wolbachia endobacteria were extremely abundant in the hypodermis (figure 3a). Neutrophils adjacent to the cuticle were frequently observed undergoing degranulation in the CON group, although this did not cause any discernible damage (figure 3b). In the MEL group, Wolbachia remained at high densities in the hypodermal cords (figure 3c) in worms that were not in the advanced stages of resorption. Eosinophils were occasionally seen close to the cuticle, but degranulation was very infrequent and the outer layers of the cuticle remained unmodified (figure 3d). By contrast, the ultrastructure of nodules in the OXY group at 12 wpt revealed unique alterations. Eosinophil degranulation in direct contact with the worm cuticle was common and associated with pronounced deformation of the outer cuticular layers (figure 3e). Furthermore, parasite integrity was clearly compromised, as eosinophils could be observed free within the body cavity of the worms (figure 3f).Figure 3.


A worm's best friend: recruitment of neutrophils by Wolbachia confounds eosinophil degranulation against the filarial nematode Onchocerca ochengi.

Hansen RD, Trees AJ, Bah GS, Hetzel U, Martin C, Bain O, Tanya VN, Makepeace BL - Proc. Biol. Sci. (2010)

Ultrastructure of O. ochengi onchocercomata at 12 weeks. (a) Hypodermis of an untreated worm showing abundant Wolbachia endosymbionts (W). (b) The cuticle (C) of an untreated worm displaying normal structure, alongside an adherent neutrophil (N) surrounded by numerous extracellular granules (EG). (c) A worm section from the melarsomine (MEL) group displaying intact Wolbachia (W) beneath the hypodermal lamellae (HL) and the cuticle (C). (d) Eosinophils (E) attached to Splendore-Hoeppli deposits (SH) on the cuticle (C) of a worm from the MEL group. (e) The pseudopodium (P) of a degranulating eosinophil (DE) entering a cleft in the cuticle (C) of an oxytetracycline (OXY)-treated worm. (f) Two eosinophils (E) adjacent to the paired uteri (U) within the pseudocoelomic cavity of a worm from the OXY group; eosinophils are also visible on the host side of the cuticular (C) interface. Note the highly vacuolated hypodermis. Scale bars: (a–e) 2 µm; (f)10 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3119012&req=5

RSPB20102367F3: Ultrastructure of O. ochengi onchocercomata at 12 weeks. (a) Hypodermis of an untreated worm showing abundant Wolbachia endosymbionts (W). (b) The cuticle (C) of an untreated worm displaying normal structure, alongside an adherent neutrophil (N) surrounded by numerous extracellular granules (EG). (c) A worm section from the melarsomine (MEL) group displaying intact Wolbachia (W) beneath the hypodermal lamellae (HL) and the cuticle (C). (d) Eosinophils (E) attached to Splendore-Hoeppli deposits (SH) on the cuticle (C) of a worm from the MEL group. (e) The pseudopodium (P) of a degranulating eosinophil (DE) entering a cleft in the cuticle (C) of an oxytetracycline (OXY)-treated worm. (f) Two eosinophils (E) adjacent to the paired uteri (U) within the pseudocoelomic cavity of a worm from the OXY group; eosinophils are also visible on the host side of the cuticular (C) interface. Note the highly vacuolated hypodermis. Scale bars: (a–e) 2 µm; (f)10 µm.
Mentions: In worm sections from the CON group at 12 wpt, Wolbachia endobacteria were extremely abundant in the hypodermis (figure 3a). Neutrophils adjacent to the cuticle were frequently observed undergoing degranulation in the CON group, although this did not cause any discernible damage (figure 3b). In the MEL group, Wolbachia remained at high densities in the hypodermal cords (figure 3c) in worms that were not in the advanced stages of resorption. Eosinophils were occasionally seen close to the cuticle, but degranulation was very infrequent and the outer layers of the cuticle remained unmodified (figure 3d). By contrast, the ultrastructure of nodules in the OXY group at 12 wpt revealed unique alterations. Eosinophil degranulation in direct contact with the worm cuticle was common and associated with pronounced deformation of the outer cuticular layers (figure 3e). Furthermore, parasite integrity was clearly compromised, as eosinophils could be observed free within the body cavity of the worms (figure 3f).Figure 3.

Bottom Line: In this study, cattle infected with Onchocerca ochengi received adulticidal regimens of oxytetracycline or melarsomine.In contrast to oxytetracycline, melarsomine did not directly affect Wolbachia viability.Taken together, these data offer strong support for the hypothesis that Wolbachia confers longevity on O. ochengi through a defensive mutualism, which diverts a potentially lethal effector cell response.

View Article: PubMed Central - PubMed

Affiliation: Liverpool School of Tropical Medicine, School of Veterinary Science and Institute of Infection and Global Health, University of Liverpool, , Liverpool L69 7ZJ, UK.

ABSTRACT
Onchocerca ochengi, a filarial parasite of cattle, represents the closest relative of the human pathogen, Onchocerca volvulus. Both species harbour Wolbachia endosymbionts and are remarkable in that adult female worms remain viable but sessile for many years while surrounded by host cells and antibodies. The basis of the symbiosis between filariae and Wolbachia is thought to be metabolic, although a role for Wolbachia in immune evasion has received little attention. Neutrophils are attracted to Wolbachia, but following antibiotic chemotherapy they are replaced by eosinophils that degranulate on the worm cuticle. However, it is unclear whether the eosinophils are involved in parasite killing or if they are attracted secondarily to dying worms. In this study, cattle infected with Onchocerca ochengi received adulticidal regimens of oxytetracycline or melarsomine. In contrast to oxytetracycline, melarsomine did not directly affect Wolbachia viability. Eosinophil degranulation increased significantly only in the oxytetracycline group; whereas nodular gene expression of bovine neutrophilic chemokines was lowest in this group. Moreover, intense eosinophil degranulation was initially associated with worm vitality, not degeneration. Taken together, these data offer strong support for the hypothesis that Wolbachia confers longevity on O. ochengi through a defensive mutualism, which diverts a potentially lethal effector cell response.

Show MeSH
Related in: MedlinePlus