Protection against Mycobacterium ulcerans Lesion Development by Exposure to Aquatic Insect Saliva

Abstract

BackgroundBuruli 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 FindingsWe 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.ConclusionsThese 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.

Environmental and Health-Related Risk Factors for Mycobacterium ulcerans Disease (Buruli Ulcer) in Benin

“…In contrast to previous reports, access to drinkable water 1 did not seem to be associated with BU, and our data do not suggest that wearing clothes during farming activities is protective against BU. This could fit with the hypothesis of a possible immune protection against BU provided by frequent insect bites, 8 but the most likely explanation is that subjects with BU typically wear clothes to hide skin lesions. Our data were collected through a questionnaire.…”

Bacterial strategies to overcome insect defences

“…Mycobacterium ulcerans, the causative agent of Buruli ulcer, colonizes the salivary glands of N. cimicoides. Between 5% and 10% of N. cimicoides that are captured in endemic areas are infected with M. ulcerans 88 . Immediately after ingestion, M. ulcerans translocates from the head capsule to the coelomic cavity.…”

Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model

“…It has been demonstrated that animals preexposed to ticks were protected from tularemia (15) and borreliosis (16,17), and vaccination with a tick salivary cement protein protected mice against the lethal effect of tick-borne encephalitis virus (18). Preexposure to mosquito saliva through bites led to partial protection against Plasmodium berghei infection (19) and immunization with the saliva of an aquatic insect (Naucoris genus) protected mice against Mycobacterium ulcerans infection (20).…”