MURINE INTRANASAL CHALLENGE MODEL FOR THE STUDY OF CAMPYLOBACTER PATHOGENESIS AND IMMUNITY

Campylobacter jejuni infection of mice initiated by intranasal adminis tration was investigated as a potential model for studies of pathogene sis and immunity, By using a standard challenge (5 x 10(9) CFU), C. je juni 81-176 was more virulent for BALB/c (72% mortality) than for C3H/ Hej (50%), CBA/CAJ (30%), or C58/J (0%), Intranasal challenge of BALB/ c was used to compare the relative virulence of three reference strain s; C. jejuni 81-176 was more virulent (killing 83% of challenged mice) than C. jejuni HC (0%) or C. coli VC-167 (0%), The course of intranas ally initiated C. jejuni 81-176 infection in BALB/c was determined, C. jejuni was recovered from the lungs, intestinal tract, liver, and spl een at 4 h after challenge, the first interval evaluated, After this i nitial interval, three distinct patterns of infection were recognized: (i) a progressive decline in number of C. jejuni CFU (stomach, blood, lungs), (ii) decline followed by a second peak in the number of organ isms recovered at 2 or 3 days postchallenge (intestine, liver, mesente ric lymph nodes), and (iii) persistence of approximately the same numb er of C. jejuni CFU during the course of the experiment (spleen), Intr anasally induced infection initiated with a sublethal number of bacter ia or intranasal immunization with killed Campylobacter preparations r esulted in both the generation of Campylobacter antigen-specific immun e responses and an acquired resistance to homologous rechallenge, The model was used to evaluate the relative virulence of nine low-in vitro -passage (no more than five passages) isolates of C. jejuni species fr om patients with diarrhea, The patient isolates were differentially vi rulent for mice; one killed all exposed mice, three were avirulent (no deaths) and the remainder showed an intermediate virulence, killing 1 7 to 33%, Mouse virulence of Campylobacter strains showed a trend towa rd isolates originating from individuals with watery diarrhea; however , no association was found between mouse virulence and other signs or symptoms, There were no observed relationships between mouse virulence and bacterial Lior serotype or Fla polymorphic group. Intranasal chal lenge of BALB/c with C. jejuni is a useful model for the study of infe ction and vaccination-acquired immunity to this agent.