Immune response to and tissue localization of the Wolbachia surface protein (WSP) in dogs with natural heartworm (Dirofilaria immitis) infection

Kramer, Laura; Tamarozzi, Francesca; Morchón, Rodrigo; López-Belmonte, Juan Luis; Marcos‐Atxutegi, C.; Martín-Pacho, R.; Simón, F.

doi:10.1016/j.vetimm.2005.03.011

Cited by 51 publications

(45 citation statements)

References 21 publications

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“…Because these Drosophila flies are carrying the chic 221 mutation and we have already shown that this mutation results in a decrease in Wolbachia titer, this finding was not surprising. However, we did identify four lines for which the quantity of wsp was not statistically significantly different from the control lines (lines 19,17,16,12). In these four lines, the Wolbachia titer resembles that of the original, maternal line, although the flies carry the chic 221 mutation (Fig.…”

Section: Heterozygous Profilin Flies Harbor Low-titermentioning

confidence: 79%

Passage of Wolbachia pipientis through Mutant Drosophila melanogaster Induces Phenotypic and Genomic Changes

Newton

Sheehan

2015

Appl Environ Microbiol

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Wolbachia pipientis is a nearly ubiquitous, maternally transmitted bacterium that infects the germ line of insect hosts. Estimates are that Wolbachia infects 40 to 60% of insect species on the planet, making it one of the most prevalent infections on Earth. However, we know surprisingly little about the molecular mechanisms used by Wolbachia to infect its hosts. We passaged Wolbachia through normally restrictive Drosophila melanogaster hosts, bottlenecking Wolbachia through stochastic segregation while simultaneously selecting for mutants that could recolonize these previously restrictive hosts. Here, we show that Wolbachia alters its behavior when passaged through heterozygous mutant flies. After only three generations, Wolbachia was able to colonize the previously restrictive hosts at control titers. Additionally, the Wolbachia organisms passaged through heterozygous mutant D. melanogaster alter their pattern of tissue-specific Wsp protein production, suggesting a behavioral response to the host genotype. Using whole-genome resequencing, we identified the mutations accumulated by these lineages of Wolbachia and confirmed the existence and persistence of the mutations through clone library Sanger sequencing. Our results suggest that Wolbachia can quickly adapt to new host contexts, with genomic mutants arising after only two generations. Wolbachia pipientis is an obligate intracellular member of Alphaproteobacteria that forms symbioses with an extremely broad array of hosts (1). Wolbachia infections are considered a "pandemic" in insects, and estimates suggest that upwards of 40% of insect species are infected by the bacterial parasite (2, 3). Wolbachia is well known for reproductive effects induced in the host, which range from the exotic (male killing) to the most common of reproductive effects: cytoplasmic incompatibility (CI) (1). In CI, infected females can breed with either infected or uninfected males, but uninfected females cannot breed with infected males. This results in a drop in fecundity for uninfected females, allowing Wolbachia to spread effectively through new insect populations via maternal transmission (1, 4).Because Wolbachia is obligately intracellular and not genetically tractable, the research community has turned to genomic sequencing to identify potential mechanisms behind host interaction. Even closely related Wolbachia strains (based on multilocus [MLST] profiles) exhibit significant genomic diversity (5). That is, between related hosts, Wolbachia strains can differ substantially in terms of both genomic content and divergence of orthologous genes (6). In an attempt to identify the loci involved in the induction of different reproductive phenotypes, Wolbachia strains that infect different hosts (7) or cause different reproductive phenotypes (8) have been compared, and the loci have been correlated with those phenotypes. In order to pinpoint the mechanism behind pathogen blocking, Wolbachia variants that are more or less pathogenic or protect the host against viruses to a lesser or grea...

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Section: Heterozygous Profilin Flies Harbor Low-titermentioning

confidence: 79%

Passage of Wolbachia pipientis through Mutant Drosophila melanogaster Induces Phenotypic and Genomic Changes

Newton

Sheehan

2015

Appl Environ Microbiol

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“…Even though arteritis and thromboembolic disease secondary to the presence of adult D. immitis in the pulmonary arteries could explain a few of the manifestations of feline filarial disease at postmortem examination, it was nevertheless demonstrated that severe pulmonary lesions occur in the absence of adult worms (5,8). Macrophages containing Wolbachia have been found in the lungs, kidneys, and liver, of dogs infected with D. immitis (18). Evidence suggests that, in cats, even transient filarial infections cause enduring and even worsening lung lesions (4).…”

Section: Figmentioning

confidence: 99%

“…Lung lesions are typically characterized by both parenchymal and vascular inflammation evolving into arteriolar occlusive hypertrophy. Typically, the WSP antigen was demonstrated in lung lesions (8,17,18). The WSP antigen of Wolbachia elicits a strong inflammatory response itself in the host, so a pivotal role in the HARD syndromes was hypothesized (24).…”

Section: Figmentioning

confidence: 99%

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Detection of Wolbachia DNA in Blood for Diagnosing Filaria-Associated Syndromes in Cats

et al. 2012

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A fundamental role for the endosymbiotic bacteria Wolbachia pipientis in the pathogenesis of Dirofilaria immitis infections has emerged in recent years. Diagnostic opportunities arising from this breakthrough have not yet been fully exploited. This study was aimed at developing conventional and real-time PCR assays to carry out a molecular survey in a convenience sample of cats living in an area where D. immitis is endemic and to evaluate the detection of bacterial DNA in blood as a surrogate assay for diagnosing filaria-associated syndromes in cats. COI and FtsZ loci were used as targets for D. immitis and Wolbachia PCR assays, respectively, and real-time TaqMan PCR assays were used only for Wolbachia. A convenience sample of 307 disease-affected or healthy cats examined at a University facility were PCR tested, and their medical records were investigated. Conventional nested PCR for Wolbachia amplified the endosymbionts of both D. immitis and D. repens, while real-time PCR was highly specific only for the former. Observed prevalences of 0.3 and 10.4% were found using conventional nested PCR assays for D. immitis and real-time PCR for Wolbachia, respectively. Similar prevalences were established using the Wolbachia nested PCR (98% concordance with real-time PCR). The group of Wolbachia-positive samples had a significantly higher proportion of subjects with respiratory signs (29.0% versus 9.7%; P ‫؍‬ 0.002). The findings of this study indicate that a highly sensitive PCR assay can be used to detect the Wolbachia organism in the peripheral blood of cats with respiratory signs.

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“…In human D. immitis infections, high levels of immunoglobulin G (IgG) antibodies against the Wolbachia surface protein (WSP) have consistently been detected in patients with pulmonary dirofilariosis, while in healthy donors living in areas of endemicity, the levels of IgG anti-WSP are much lower (18). In addition, Wolbachia bacteria play an important role in the immunopathogenesis of both human filarial diseases (3,19) and animal dirofilariosis (9). Eicosanoids are lipid mediators that regulate different physiological processes and modulate inflammatory and immunological responses in mammals (4).…”

mentioning

confidence: 99%

High Levels of Serum Thromboxane B2 Are Generated during Human Pulmonary Dirofilariosis

Morchón

López-Belmonte

Rodríguez-Barbero

et al. 2006

Clin Vaccine Immunol

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The canine parasite Dirofilaria immitis can infect humans. Patients with pulmonary dirofilariosis develop significantly higher thromboxane B2 levels than healthy individuals living in areas where dirofilariosis is endemic and in areas where dirofilariosis is not endemic. The possible role of Wolbachia bacteria in the appearance of this eicosanoid is discussed.Heartworm disease caused by Dirofilaria immitis in dogs and cats is distributed in temperate, subtropical, and tropical areas worldwide (7). The infection is transmitted by several mosquito species, most of which are able to feed on both animal reservoirs and humans. Thus, in areas of endemicity, people are at risk of infection. Human dirofilariosis is radiologically characterized by a solitary pulmonary calcified or noncalcified nodule (5, 15). These nodules appear when a migrating immature worm is trapped in a branch of the pulmonary artery and dies, causing coagulation necrosis with fibrosis and infiltration of inflammatory cells (8,16). Wolbachia symbiont bacteria are a stable and abundant component of the bodies of many filarial species (2). In human D. immitis infections, high levels of immunoglobulin G (IgG) antibodies against the Wolbachia surface protein (WSP) have consistently been detected in patients with pulmonary dirofilariosis, while in healthy donors living in areas of endemicity, the levels of IgG anti-WSP are much lower (18). In addition, Wolbachia bacteria play an important role in the immunopathogenesis of both human filarial diseases (3, 19) and animal dirofilariosis (9). Eicosanoids are lipid mediators that regulate different physiological processes and modulate inflammatory and immunological responses in mammals (4). The effects of some of these eicosanoids antagonize the effects of others. Specifically, the thromboxanes (Txs) constrict blood vessels, suppress cyclic AMP, and promote platelet aggregation, while leukotrienes (LTs) are related to vascular permeability, chemotaxis, and polymorphonuclear leukocyte activation (17). Some of these lipid mediators have been observed in lymphatic filariae (10,11,13) and Onchocerca volvulus (4). Clinical studies have demonstrated high concentrations of TxB2 in the plasma of patients with septic and endotoxic shock (1) and in patients with chronic obstructive pulmonary disease (6).The aim of this study was to investigate the levels of eicosanoids in the sera of patients with pulmonary dirofilariosis, a disease characterized by the inflammatory obstruction of pulmonary arteries and a disease in which the Wolbachia symbiont bacteria stimulate the immune systems of infected individuals.Eighty human serum samples were divided into three groups. Group 1 (G1; n ϭ 10) comprised serum samples from patients diagnosed with pulmonary dirofilariosis caused by D. immitis (these samples were kindly provided by Patrick Lammie from the Centers for Disease Control and Prevention, Atlanta, Ga.). These samples have high levels of specific IgG against WSP, as demonstrated previously (18). Group 2 (G2; n ϭ 40) compr...

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Immune response to and tissue localization of the Wolbachia surface protein (WSP) in dogs with natural heartworm (Dirofilaria immitis) infection

Cited by 51 publications

References 21 publications

Passage of Wolbachia pipientis through Mutant Drosophila melanogaster Induces Phenotypic and Genomic Changes

Passage of Wolbachia pipientis through Mutant Drosophila melanogaster Induces Phenotypic and Genomic Changes

Detection of Wolbachia DNA in Blood for Diagnosing Filaria-Associated Syndromes in Cats

High Levels of Serum Thromboxane B2 Are Generated during Human Pulmonary Dirofilariosis

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