Campylobacter jejuni is not merely a commensal in commercial broiler chickens and affects bird welfare

Abstract

Campylobacter jejuni is the leading cause of bacterial food-borne infection; chicken meat is its main source. C. jejuni is considered commensal in chickens based on experimental models unrepresentative of commercial production. Here we show that the paradigm of Campylobacter commensalism in the chicken is flawed. Through experimental infection of four commercial breeds of broiler chickens, we show that breed has a significant effect on C. jejuni infection and the immune response of the animals, although these factors have limited impact on the number of bacteria in chicken ceca. All breeds mounted an innate immune response. In some breeds, this response declined when interleukin-10 was expressed, consistent with regulation of the intestinal inflammatory response, and these birds remained healthy. In another breed, there was a prolonged inflammatory response, evidence of damage to gut mucosa, and diarrhea. We show that bird type has a major impact on infection biology of C. jejuni. In some breeds, infection leads to disease, and the bacterium cannot be considered a harmless commensal. These findings have implications for the welfare of chickens in commercial production where C. jejuni infection is a persistent problem. Importance: Campylobacter jejuni is the most common cause of food-borne bacterial diarrheal disease in the developed world. Chicken is the most common source of infection. C. jejuni infection of chickens had previously not been considered to cause disease, and it was thought that C. jejuni was part of the normal microbiota of birds. In this work, we show that modern rapidly growing chicken breeds used in intensive production systems have a strong inflammatory response to C. jejuni infection that can lead to diarrhea, which, in turn, leads to damage to the feet and legs on the birds due to standing on wet litter. The response and level of disease varied between breeds and is related to regulation of the inflammatory immune response. These findings challenge the paradigm that C. jejuni is a harmless commensal of chickens and that C. jejuni infection may have substantial impact on animal health and welfare in intensive poultry production:

FIG 1

Expression of proinflammatory cytokines and chemokines in cecal tissue following C. jejuni M1 infection. (a to c) Fold changes in expression of chemokines CXCLi1 (a) and CXCLi2 (b) and cytokine IL-1β (c) in cecal tissue were examined at 2 (i), 5 (ii), and 12 (iii) dpi. At each time point, group sizes were as follows for the different breeds: n = 10 for breed A1, n = 9 for breed A2, n = 10 for breed B1, and n = 10 for breed B2. Each symbol represents the value for an individual chicken. A white bar represents the median value for each group. Significance of differences between the groups was examined using a Kruskal-Wallis test.

FIG 2

Expression of proinflammatory chemokine CXCLi2 in ileal tissue following C. jejuni M1 infection. (a to c) Fold changes in expression of CXCLi2 in ileal tissue were examined at 2 (a), 5 (b), and 12 (c) dpi. At each time point, group sizes were as follows for the different breeds: n = 10 for breed A1, n = 9 for breed A2, n = 10 for breed B1, and n = 10 for breed B2. Each symbol represents the value for an individual chicken. A white bar represents the median value for each group. Significance of differences between the groups was examined using a Kruskal-Wallis test.

FIG 3

Histological features in control and infected animals at day 5 postinfection. (A to D) Ileum sections from chickens. (A and B) Uninfected control animals of breed A1 (A) and B2 (B). Slim, slender villi with moderate (score 2) lymphocyte and plasma cell infiltration and mild (score 1) heterophil infiltration. (C and D) Infected animals. Villi are thickened (score 2) due to marked (score 3) lymphocyte and plasma cell infiltration and moderate (score 2) heterophil infiltration (arrows) and appear slightly shorter. (E to H) Cecum sections from breed A1 (E and F) and B2 (G and H). Control animals (E and G) exhibit moderate (score 2) lymphocyte and plasma cell infiltration and mild heterophil (score 1) infiltration. In infected animals (F and H), there is increased leukocyte infiltration, with marked (score 3) lymphocyte and plasma cell infiltration and moderate (score 2) heterophil infiltration.

FIG 4

Expression of T_H1 and regulatory cytokines in cecal tissue following C. jejuni M1 infection. (a) Fold changes in expression of the regulatory cytokine IL-10 in tissue were examined at 12 dpi. (b) Fold changes in expression of the T_H1-biased cytokine IFN-γ were also examined at 12 dpi. At each time point, group sizes were as follows for the different breeds: n = 10 for breed A1, n = 9 for breed A2, n = 10 for breed B1, and n = 10 for breed B2. Each symbol represents the value for an individual chicken. A white bar represents the median value for each group. Significance of differences between the groups was examined using a Kruskal-Wallis test.