title: Protection against Mycobacterium ulcerans lesion development by exposure to aquatic insect saliva.
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.
  
  
  RESULTS
  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.
authors.affiliation: Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France. laurentmarsollier@hotmail.com
authors.forename: Laurent
authors.initials: L
authors.lastname: Marsollier
authors.forename: Estelle
authors.initials: E
authors.lastname: Deniaux
authors.forename: Priscille
authors.initials: P
authors.lastname: Brodin
authors.forename: Agnès
authors.initials: A
authors.lastname: Marot
authors.forename: Christelle Mbondji
authors.initials: CM
authors.lastname: Wondje
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Saint-André
authors.forename: Annick
authors.initials: A
authors.lastname: Chauty
authors.forename: Christian
authors.initials: C
authors.lastname: Johnson
authors.forename: Fredj
authors.initials: F
authors.lastname: Tekaia
authors.forename: Edouard
authors.initials: E
authors.lastname: Yeramian
authors.forename: Pierre
authors.initials: P
authors.lastname: Legras
authors.forename: Bernard
authors.initials: B
authors.lastname: Carbonnelle
authors.forename: Gilles
authors.initials: G
authors.lastname: Reysset
authors.forename: Sara
authors.initials: S
authors.lastname: Eyangoh
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
authors.forename: Jacques
authors.initials: J
authors.lastname: Aubry
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000941:Antigens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D004199:Disease Vectors; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007299:Insect Bites and Stings / Q000382:microbiology; D007313:Insecta / Q000276:immunology* / Q000382:microbiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology / Q000635:transmission; D019911:Mycobacterium ulcerans / Q000276:immunology*; D012463:Saliva / Q000276:immunology* / Q000382:microbiology; D012883:Skin Ulcer / Q000382:microbiology*
chemical_list: D000941:Antigens; D007074:Immunoglobulin G