Detection of Serum IgG Antibodies Specific for<i>Wolbachia</i>Surface Protein in Rhesus Monkeys Infected with<i>Brugia malayi</i>

Punkosdy, George A.; Dennis, Vida A.; Lasater, Barbara L.; Tzertzinis, George; Foster, Jeremy M.; Lammie, Patrick J.

doi:10.1086/322023

Cited by 51 publications

(48 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Bazzocchi et al (5) reported the universal production of anti-WSP antibodies in Dirofilaria immitis-infected cats, suggesting that the constant release of Wolbachia organisms through natural worm death was sufficient to induce an antibody response. In contrast, others have reported an increase in antibodies to WSP in two B. malayi-infected rhesus monkeys only at the time of transition from microfilaremic to amicrofilaremic status and during attacks of lymphedema (41).…”

Section: Discussionmentioning

confidence: 69%

“…Gerbils were bled throughout the course of infection and at necropsy. Blood was examined for microfilariae, and sera were harvested for the analysis of antibodies against Wolbachia surface protein (WSP) (41). Necropsies and worm recoveries were performed at 76, 86, and 100 DPI.…”

Section: Gerbils and Parasitesmentioning

confidence: 99%

“…Sera collected weekly from all gerbils were analyzed for the presence of anti-WSP antibodies at 0, 8, 17, 23, 43, 58, and 86 DPI. Recombinant WSP was produced in bacteria, purified by column chromatography (41), and used to coat 96-well plates at 0.5 g/ml. Plates were blocked with 0.3% PBST (0.1 M PBS plus 0.3% Tween 20) for 1 h at 4°C, and then sera (diluted 1:50 in 0.05% PBST) were applied in duplicate and incubated for 2 h at room temperature.…”

Section: Vol 71 2003mentioning

confidence: 99%

See 2 more Smart Citations

Removal of Wolbachia from Brugia pahangi Is Closely Linked to Worm Death and Fecundity but Does Not Result in Altered Lymphatic Lesion Formation in Mongolian Gerbils ( Meriones unguiculatus )

Chirgwin¹,

Coleman²,

Porthouse³

et al. 2003

Infect Immun

View full text Add to dashboard Cite

Approximately 30 years ago, researchers reported intracellular bacteria in filarial nematodes. These bacteria are relatives of the arthropod symbiont Wolbachia and occur in many filarial nematodes, including Brugia pahangi and Brugia malayi. Wolbachia bacteria have been implicated in a variety of roles, including filaria development and fecundity and the pathogenesis of lymphatic lesions associated with filarial infections. However, the role of the bacteria in worm biology or filarial disease is still not clear. The present experiments support previous data showing that tetracycline eliminates or reduces Wolbachia bacteria in B. pahangi in vivo. The elimination of Wolbachia was closely linked to a reduction in female fecundity and the viability of both sexes, suggesting that the killing of Wolbachia is detrimental to B. pahangi. The gerbils treated with tetracycline showed reduced levels of interleukin-4 (IL-4) and IL-5 mRNA in renal lymph nodes and spleens compared with the levels in B. pahangi-infected gerbils not treated with tetracycline. However, similar findings were noted in B. pahangi-infected gerbils treated with ivermectin, suggesting that the loss of circulating microfilariae, not the reduction of Wolbachia bacteria, was associated with the altered cytokine profile. Despite the change in T-cell cytokines, there was no difference in the sizes of renal lymph nodes isolated from gerbils in each treatment group. Furthermore, the numbers, sizes, or cellular compositions of granulomas examined in the lymphatics or renal lymph nodes did not differ with treatment. These data suggest that Wolbachia may not play a primary role in the formation of lymphatic lesions in gerbils chronically infected with B. pahangi.Lymphatic filariasis is caused primarily by the filarial nematodes Wuchereria bancrofti and Brugia malayi and affects more than 120 million people throughout the tropics and subtropics. The disease presents as a broad range of clinical and subclinical symptoms, including fever, acute and chronic inflammation, lymphatic edema, and elephantiasis. While much research has focused on the disease caused by infection with Brugia or Wuchereria, the mechanism(s) underlying the pathogenesis of lymphatic filariasis has not been clearly defined. In both acute and chronic infections, these mechanisms probably involve a diverse range of inflammatory reactions attributable to the parasite, host inflammatory responses, and opportunistic infections (40).Approximately 30 years ago, several researchers reported intracellular bacteria in filarial nematodes (31, 37, 54). These bacteria have since been identified as relatives of the arthropod symbiont Wolbachia (46). Wolbachia bacteria have now been reported to exist in many filarial nematodes, including B. malayi and Brugia pahangi (3,30,49,55). Interestingly, Wolbachia has recently been proposed to play a role in the induction of the host immune response to filariae (9,44,50,51). Some researchers suggest that lipopolysaccharide (LPS)-like molecules from filarial Wolbachia b...

show abstract

Section: Discussionmentioning

confidence: 69%

Section: Gerbils and Parasitesmentioning

confidence: 99%

Section: Vol 71 2003mentioning

confidence: 99%

See 1 more Smart Citation

Removal of Wolbachia from Brugia pahangi Is Closely Linked to Worm Death and Fecundity but Does Not Result in Altered Lymphatic Lesion Formation in Mongolian Gerbils ( Meriones unguiculatus )

Chirgwin¹,

Coleman²,

Porthouse³

et al. 2003

Infect Immun

View full text Add to dashboard Cite

show abstract

“…Furthermore, Wolbachia is not the target of the antibody response in immunized wild-type or TLR4-mutant mice, suggesting that the immune response does not target Wolbachia in order to mediate larval killing. Even though the antibody response against Wolbachia proteins may be an effective way to determine disease outcome for lymphatic filariasis (28,29), it appears to be a poor indicator of protective immunity against larval O. volvulus in mice.…”

Section: Discussionmentioning

confidence: 99%

Protective Immunity to the Larval Stages ofOnchocerca volvulusIs Dependent on Toll-Like Receptor 4

et al. 2005

View full text Add to dashboard Cite

Toll-like receptor 4 (TLR4) has been shown to be important for the induction of Th2-dependent immune responses in mice. Protective immunity against larval Onchocerca volvulus in mice depends on the development of a Th2 immune response mediated by both interleukin-4 (IL-4) and IL-5. In addition, O. volvulus contains the rickettsial endosymbiont Wolbachia, which has molecules with lipopolysaccharide-like activities that also signal through TLR4. We therefore hypothesized that protective immunity to O. volvulus would not develop in C3H/HeJ mice which have a mutation in the Tlr4 gene (TLR4 mutant), either because of a decreased Th2 response to the larvae or because of the absence of a response to Wolbachia. TLR4-mutant mice were immunized against O. volvulus with irradiated third-stage larvae, and it was observed that Th2 responses were elevated based on increased IL-5 production, total immunoglobulin E (IgE) levels, antigen-specific IgG1 response, and eosinophil recruitment. Protective immunity, however, did not develop in the TLR4-mutant mice. The Th1 response, as measured by gamma interferon production from spleen cells, was comparable in both wild-type and TLR4-mutant mice. Furthermore, antibody responses to Wolbachia were absent in both wild-type and TLR4-mutant mice. Therefore, the defect in the development of a protective immune response against O. volvulus in TLR4-mutant mice is not due to loss of Th2 immunity or the response to Wolbachia but is due to an unidentified TLR4-dependent larval killing mechanism.

show abstract

“…The mechanisms underlying the inflammation induced by filarial infection are poorly understood, but studies of humans with natural infection and experimental animals exposed to live filaria or soluble extracts of the organisms have implicated a role for both adaptive and innate immunity (1)(2)(3). The remarkable observation that W. bancrofti, B. malayi, and O. volvulus harbor endosymbiotic Wolbachia bacteria (4 -6) has raised the possibility that infected individuals respond to these organisms in addition to nematode ligands and that Wolbachia can initiate or promote inflammation (7)(8)(9)(10)(11)(12). Despite remarkable longevity in the human host (13), adult filarial worms themselves are not strong inducers of inflammation (3,14).…”

mentioning

confidence: 99%

Innate Immune Responses to Endosymbiotic Wolbachia Bacteria in Brugia malayi and Onchocerca volvulus Are Dependent on TLR2, TLR6, MyD88, and Mal, but Not TLR4, TRIF, or TRAM

Hise

Daehnel

Gillette‐Ferguson

et al. 2007

The Journal of Immunology

106

View full text Add to dashboard Cite

The discovery that endosymbiotic Wolbachia bacteria play an important role in the pathophysiology of diseases caused by filarial nematodes, including lymphatic filariasis and onchocerciasis (river blindness) has transformed our approach to these disabling diseases. Because these parasites infect hundreds of millions of individuals worldwide, understanding host factors involved in the pathogenesis of filarial-induced diseases is paramount. However, the role of early innate responses to filarial and Wolbachia ligands in the development of filarial diseases has not been fully elucidated. To determine the role of TLRs, we used cell lines transfected with human TLRs and macrophages from TLR and adaptor molecule-deficient mice and evaluated macrophage recruitment in vivo. Extracts of Brugia malayi and Onchocerca volvulus, which contain Wolbachia, directly stimulated human embryonic kidney cells expressing TLR2, but not TLR3 or TLR4. Wolbachia containing filarial extracts stimulated cytokine production in macrophages from C57BL/6 and TLR4−/− mice, but not from TLR2−/− or TLR6−/− mice. Similarly, macrophages from mice deficient in adaptor molecules Toll/IL-1R domain-containing adaptor-inducing IFN-β and Toll/IL-1R domain-containing adaptor-inducing IFN-β-related adaptor molecule produced equivalent cytokines as wild-type cells, whereas responses were absent in macrophages from MyD88−/− and Toll/IL-1R domain-containing adaptor protein (TIRAP)/MyD88 adaptor-like (Mal) deficient mice. Isolated Wolbachia bacteria demonstrated similar TLR and adaptor molecule requirements. In vivo, macrophage migration to the cornea in response to filarial extracts containing Wolbachia was dependent on TLR2 but not TLR4. These results establish that the innate inflammatory pathways activated by endosymbiotic Wolbachia in B. malayi and O. volvulus filaria are dependent on TLR2-TLR6 interactions and are mediated by adaptor molecules MyD88 and TIRAP/Mal.

show abstract

Detection of Serum IgG Antibodies Specific forWolbachiaSurface Protein in Rhesus Monkeys Infected withBrugia malayi

Cited by 51 publications

References 15 publications

Removal of Wolbachia from Brugia pahangi Is Closely Linked to Worm Death and Fecundity but Does Not Result in Altered Lymphatic Lesion Formation in Mongolian Gerbils ( Meriones unguiculatus )

Removal of Wolbachia from Brugia pahangi Is Closely Linked to Worm Death and Fecundity but Does Not Result in Altered Lymphatic Lesion Formation in Mongolian Gerbils ( Meriones unguiculatus )

Protective Immunity to the Larval Stages ofOnchocerca volvulusIs Dependent on Toll-Like Receptor 4

Innate Immune Responses to Endosymbiotic Wolbachia Bacteria in Brugia malayi and Onchocerca volvulus Are Dependent on TLR2, TLR6, MyD88, and Mal, but Not TLR4, TRIF, or TRAM

Contact Info

Product

Resources

About