Promotion of ulcerative duodenitis in young ferrets by oral immunization with Helicobacter mustelae and muramyl dipeptide.
BACKGROUND
The purpose of this study was to determine whether oral immunization of ferret kits with a whole-cell sonicate of Helicobacter mustelae lysate (Hml) and the adjuvant muramyl dipeptide (MDP) would reduce the incidence of natural colonization with H. mustelae and the extent of Helicobacter-associated gastritis by enhancing the host mucosal immune response.


METHODS
Between the ages of 4 and 11 weeks, 44 ferret kits were gavaged with Hml and various doses of MDP. The extent of gastritis and duodenitis and the immune response to H. mustelae were evaluated.


RESULTS
All kits became colonized naturally with H. mustelae and the majority developed mild to severe gastritis and duodenitis. Kits that received Hml with MDP developed significantly greater inflammation of the gastric antrum and duodenum, as compared to kits vaccinated with Hml alone. Vaccination with Hml and 50 micrograms of MDP was associated with severe lesions in the proximal duodenum characterized by accumulation of mononuclear inflammatory cells, mucosal erosion, and ulceration. Although serum antibody specific for H. mustelae in 4-week-old kits was approximately 50% of adult levels, a finding attributable to passively acquired maternal antibody, both systemic and mucosal antibody levels became depressed over time despite oral vaccination. The humoral immune response was sufficiently low to prevent detection of any significant dose effect of MDP on antibody levels among experimental groups.


CONCLUSIONS
Oral vaccination of young ferrets with Hml and 50 micrograms MDP increased the risk of Helicobacter-associated mucosal ulceration in the proximal duodenum, which was associated with low humoral (but significant cell-mediated) immune responses to H. mustelae. In retrospect, the frequency of vaccination may have suppressed the systemic humoral immune response, thereby promoting mucosal damage by H. mustelae. The 50-microgram dose of MDP enhanced the cell-mediated immune response, which indirectly contributed to development of severe lesions. The increased frequency of mucosal damage associated with this vaccination regimen enhances the value of the ferret model for studying duodenal ulceration secondary to Helicobacter infection.
Whary
M T
MT
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge 02139, USA.
Palley
L S
LS
Batchelder
M
M
Murphy
J C
JC
Yan
L
L
Taylor
N S
NS
Fox
J G
JG
D000119:Acetylmuramyl-Alanyl-Isoglutamine; D000276:Adjuvants, Immunologic; D000818:Animals; D004382:Duodenitis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005289:Ferrets; D016998:Helicobacter / Q000276:immunology*; D016481:Helicobacter Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology; D007114:Immunization
D000276:Adjuvants, Immunologic; D000119:Acetylmuramyl-Alanyl-Isoglutamine