Murine intranasal challenge model for the study of Campylobacter pathogenesis and immunity

Abstract

Campylobacter jejuni infection of mice initiated by intranasal administration was investigated as a potential model for studies of pathogenesis and immunity. By using a standard challenge (5 ؋ 10 9 CFU), C. jejuni 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 strains; 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 intranasally initiated C. jejuni 81-176 infection in BALB/c was determined. C. jejuni was recovered from the lungs, intestinal tract, liver, and spleen at 4 h after challenge, the first interval evaluated. After this initial 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 organisms recovered at 2 or 3 days postchallenge (intestine, liver, mesenteric lymph nodes), and (iii) persistence of approximately the same number of C. jejuni CFU during the course of the experiment (spleen). Intranasally induced infection initiated with a sublethal number of bacteria or intranasal immunization with killed Campylobacter preparations resulted in both the generation of Campylobacter antigen-specific immune 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 from patients with diarrhea. The patient isolates were differentially virulent for mice; one killed all exposed mice, three were avirulent (no deaths) and the remainder showed an intermediate virulence, killing 17 to 33%. Mouse virulence of Campylobacter strains showed a trend toward 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 challenge of BALB/c with C. jejuni is a useful model for the study of infection and vaccination-acquired immunity to this agent. Campylobacter jejuni is a major cause of gastroenteritis (36, 38) and enterocolitis in humans. Infection may be asymptomatic or associated with disease ranging in severity from acute watery diarrhea (13) to inflammatory disease that may be associated with a tissue invasion (26) and at times with bacteremia (19). Immunity to Campylobacter disease can develop as the result of repeated infections (11, 13, 36), and, thus, the feasibility of a vaccine for prevention of Campylobacter disease is suggested. The mechanism(s) of immune protection to Campylobacter infection and disease is poorly understood, and thus little information is available to guide vaccine development. In part, this deficit in knowledge results from the lack of an animal model of Campylobacter infect...

Long-term systemic and mucosal antibody responses measured in BALB/c mice following intranasal challenge with viable enterotoxigenicEscherichia coli

“…to mice was used in studying vaccine candidates (Turbyfill et al, 2000) and pathology similar to that observed in humans (Van De Verg et al, 1995). The intranasal route for the delivery of C. jejuni to mice was used to study infection and vaccination-acquired immunity (Baqar et al, 1996). Van De Verg et al (1995) noted the advantage of using an intranasal mouse model in the study of the immunopathogenesis of an enteric infection.…”

The route less taken: pulmonary models of enteric Gram-negative infection

“…It was proposed that IgA opsonization of Shigella in the intestinal lumen would facilitate the bactericidal activity of infiltrating neutrophils and resident macrophages and reduce bacterial infection (Phalipon et al, 1995). Supporting this model, vaccination via the intranasal or orogastric route with proteosome-LPS complex from S. sonneii cross protects against subsequent intranasal challenge with S. flexneri or S. sonneii (Mallett et al, 1995) and that protection was 1 9 10 9 2 9 10 3 -1 9 10 7 < 1 (5 dpi) Baqar et al (1996) associated with production of IgA and IL-6 (Mallett et al, 1993;Phalipon et al, 1995). More recent work has revealed that transgenic BALB/c mice expressing IgA antibodies to Shigella LPS from an implanted hybridoma are less susceptible to subsequent intranasal infection (Phalipon et al, 1995).…”

“…However, recently, a model has been developed in which SCID mice cleared of their natural flora were chronically colonized and inflammation of the gastrointestinal tissues induced, which will aid in future understanding of host response (Chang & Miller, 2006). To complement existing models of pathogenesis, an intranasal model of C. jejuni infection was developed (Table 2; Baqar et al, 1996). After intranasal inoculation of 1 9 10 9 CFU, lungs, stomach, large intestine, small intestine, liver, mesenteric lymph nodes, and spleen were all colonized by 6 h and declined over the course of 7 days.…”

“…This suggests there may have been technical differences between the two studies or laboratory-specific mutations (Al-Banna et al, 2008). The lethality in C. jejuni-infected mice, however, correlates with the severity of the symptoms of the donor patient (Baqar et al, 1996).…”

Animal models of Campylobacter jejuni colonization and disease and the lessons to be learned from similar Helicobacter pylori models

“…Although the natural route of transmission for C. jejuni is oral challenge, alternative routes to enhance virulence potential have been considered. Intranasal inoculation of adult mice caused death within 6 d postchallenge (Baqar et al 1996). The degree of lethality varied with the dose, mouse strain and campylobacter isolate used.…”