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Protection against Mycobacterium ulcerans lesion development by exposure to aquatic insect saliva.

Marsollier L, Deniaux E, Brodin P, Marot A, Wondje CM, Saint-André JP, Chauty A, Johnson C, Tekaia F, Yeramian E, Legras P, Carbonnelle B, Reysset G, Eyangoh S, Milon G, Cole ST, Aubry J - PLoS Med. (2007)

Bottom Line: Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment.Then using human serum samples collected in a Buruli ulcer-endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies.IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group.

View Article: PubMed Central - PubMed

Affiliation: Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France. laurentmarsollier@hotmail.com

ABSTRACT

Background: Buruli ulcer is a severe human skin disease caused by Mycobacterium ulcerans. This disease is primarily diagnosed in West Africa with increasing incidence. Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment. The mode of transmission of this Mycobacterium species remains a matter of debate, and relevant interventions to prevent this disease lack (i) the proper understanding of the M. ulcerans life history traits in its natural aquatic ecosystem and (ii) immune signatures that could be correlates of protection. We previously set up a laboratory ecosystem with predatory aquatic insects of the family Naucoridae and laboratory mice and showed that (i) M. ulcerans-carrying aquatic insects can transmit the mycobacterium through bites and (ii) that their salivary glands are the only tissues hosting replicative M. ulcerans. Further investigation in natural settings revealed that 5%-10% of these aquatic insects captured in endemic areas have M. ulcerans-loaded salivary glands. In search of novel epidemiological features we noticed that individuals working close to aquatic environments inhabited by insect predators were less prone to developing Buruli ulcers than their relatives. Thus we set out to investigate whether those individuals might display any immune signatures of exposure to M. ulcerans-free insect predator bites, and whether those could correlate with protection.

Methods and findings: We took a two-pronged approach in this study, first investigating whether the insect bites are protective in a mouse model, and subsequently looking for possibly protective immune signatures in humans. We found that, in contrast to control BALB/c mice, BALB/c mice exposed to Naucoris aquatic insect bites or sensitized to Naucoris salivary gland homogenates (SGHs) displayed no lesion at the site of inoculation of M. ulcerans coated with Naucoris SGH components. Then using human serum samples collected in a Buruli ulcer-endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies. IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group.

Conclusions: These data will help structure future investigations in Buruli ulcer-endemic areas, providing a rationale for research into human immune signatures of exposure to predatory aquatic insects, with special attention to those insect saliva molecules that bind to M. ulcerans.

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Related in: MedlinePlus

Human IgG Binding to Resident Aquatic Insect SGH by ELISA AssayMean values are indicated by arrows and are accompanied by corresponding standard deviations (in parentheses). Results from ELISAs are shown for SGH from N. flavicollis (A) and from B. cordofana (B). Comparisons by one-way analysis of variance followed by the Newman-Keuls multiple comparison test show that the relative mean titre of specific IgG in exposed individuals is significantly higher than in patients.
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pmed-0040064-g005: Human IgG Binding to Resident Aquatic Insect SGH by ELISA AssayMean values are indicated by arrows and are accompanied by corresponding standard deviations (in parentheses). Results from ELISAs are shown for SGH from N. flavicollis (A) and from B. cordofana (B). Comparisons by one-way analysis of variance followed by the Newman-Keuls multiple comparison test show that the relative mean titre of specific IgG in exposed individuals is significantly higher than in patients.

Mentions: We then carried out a quantitative analysis using ELISA (Figure 5). We detected SGH-reactive IgG antibodies in 87.2% of the exposed group (48/55) and 60% of the patient group (19/30). This difference was statistically significant (χ2 = 6.7, df = 1; p = 0.001). The relative mean titre of the SGH-binding IgG antibodies was significantly higher in the exposed group than in the patient group (p = 0.05 for N. flavicollis and p = 0.001 for B. cordofana [Newman-Keuls multiple comparison test]), suggesting a correlation between relative mean IgG antibody titre and the absence or presence of Buruli ulcers. Thus, in the sera of humans living in areas endemic for Buruli ulcers, the presence and titre value of antibodies that bind molecules derived from aquatic insect salivary glands may be potentially relevant immune biomarkers of a protective status in the absence of any preulcerative or ulcerative lesions containing M. ulcerans.


Protection against Mycobacterium ulcerans lesion development by exposure to aquatic insect saliva.

Marsollier L, Deniaux E, Brodin P, Marot A, Wondje CM, Saint-André JP, Chauty A, Johnson C, Tekaia F, Yeramian E, Legras P, Carbonnelle B, Reysset G, Eyangoh S, Milon G, Cole ST, Aubry J - PLoS Med. (2007)

Human IgG Binding to Resident Aquatic Insect SGH by ELISA AssayMean values are indicated by arrows and are accompanied by corresponding standard deviations (in parentheses). Results from ELISAs are shown for SGH from N. flavicollis (A) and from B. cordofana (B). Comparisons by one-way analysis of variance followed by the Newman-Keuls multiple comparison test show that the relative mean titre of specific IgG in exposed individuals is significantly higher than in patients.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1808094&req=5

pmed-0040064-g005: Human IgG Binding to Resident Aquatic Insect SGH by ELISA AssayMean values are indicated by arrows and are accompanied by corresponding standard deviations (in parentheses). Results from ELISAs are shown for SGH from N. flavicollis (A) and from B. cordofana (B). Comparisons by one-way analysis of variance followed by the Newman-Keuls multiple comparison test show that the relative mean titre of specific IgG in exposed individuals is significantly higher than in patients.
Mentions: We then carried out a quantitative analysis using ELISA (Figure 5). We detected SGH-reactive IgG antibodies in 87.2% of the exposed group (48/55) and 60% of the patient group (19/30). This difference was statistically significant (χ2 = 6.7, df = 1; p = 0.001). The relative mean titre of the SGH-binding IgG antibodies was significantly higher in the exposed group than in the patient group (p = 0.05 for N. flavicollis and p = 0.001 for B. cordofana [Newman-Keuls multiple comparison test]), suggesting a correlation between relative mean IgG antibody titre and the absence or presence of Buruli ulcers. Thus, in the sera of humans living in areas endemic for Buruli ulcers, the presence and titre value of antibodies that bind molecules derived from aquatic insect salivary glands may be potentially relevant immune biomarkers of a protective status in the absence of any preulcerative or ulcerative lesions containing M. ulcerans.

Bottom Line: Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment.Then using human serum samples collected in a Buruli ulcer-endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies.IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group.

View Article: PubMed Central - PubMed

Affiliation: Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France. laurentmarsollier@hotmail.com

ABSTRACT

Background: Buruli ulcer is a severe human skin disease caused by Mycobacterium ulcerans. This disease is primarily diagnosed in West Africa with increasing incidence. Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment. The mode of transmission of this Mycobacterium species remains a matter of debate, and relevant interventions to prevent this disease lack (i) the proper understanding of the M. ulcerans life history traits in its natural aquatic ecosystem and (ii) immune signatures that could be correlates of protection. We previously set up a laboratory ecosystem with predatory aquatic insects of the family Naucoridae and laboratory mice and showed that (i) M. ulcerans-carrying aquatic insects can transmit the mycobacterium through bites and (ii) that their salivary glands are the only tissues hosting replicative M. ulcerans. Further investigation in natural settings revealed that 5%-10% of these aquatic insects captured in endemic areas have M. ulcerans-loaded salivary glands. In search of novel epidemiological features we noticed that individuals working close to aquatic environments inhabited by insect predators were less prone to developing Buruli ulcers than their relatives. Thus we set out to investigate whether those individuals might display any immune signatures of exposure to M. ulcerans-free insect predator bites, and whether those could correlate with protection.

Methods and findings: We took a two-pronged approach in this study, first investigating whether the insect bites are protective in a mouse model, and subsequently looking for possibly protective immune signatures in humans. We found that, in contrast to control BALB/c mice, BALB/c mice exposed to Naucoris aquatic insect bites or sensitized to Naucoris salivary gland homogenates (SGHs) displayed no lesion at the site of inoculation of M. ulcerans coated with Naucoris SGH components. Then using human serum samples collected in a Buruli ulcer-endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies. IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group.

Conclusions: These data will help structure future investigations in Buruli ulcer-endemic areas, providing a rationale for research into human immune signatures of exposure to predatory aquatic insects, with special attention to those insect saliva molecules that bind to M. ulcerans.

Show MeSH
Related in: MedlinePlus