Campylobacter jejuni
ST353 and ST464 cause localized gut inflammation, crypt damage, and extraintestinal spread during large- and small-scale infection in broiler chickens
Authors: Chick Heather M. , Williams Lisa K. , Sparks Nick , Khattak Farina , Vermeij Paul , Frantzen Inge , Peeters Mandy , Bijlsma Jetta J. E. , John Daniel , Ogunrin Timothy , Essex Keioni , Cayrou Caroline , Kanamarlapudi Venkateswarlu , Bayliss Christopher D. , Ketley Julian M. , Humphrey Thomas J. , Rushton Steven P. , Wilkinson Thomas S. 
Published: February 2025

Campylobacter
infections in humans and chickens are a significant burden to health services and the poultry industry. In the UK, over 75% of chicken products are
Campylobacter
-positive at retail, but the knowledge of the mechanisms responsible for extraintestinal spread into edible tissues remains incomplete. This work aimed to establish if two chicken-associated lineages of
Campylobacter jejuni
, ST353 and ST464, have the potential for extraintestinal spread. Large- and small-scale chicken colonization trials investigated the infection biology of
C. jejuni
ST353 (three strains) and ST464 (four strains). Both lineages strongly colonized the ileum and ceca and were detected in liver and spleen.
C. jejuni
ST353 and ST464 spleen load were significantly increased compared to
C. jejuni
M1 controls. Immune responses in cecal tonsils exhibited early induction of IFN-γ and suppressed TGFβ at 7 days post-infection with
C. jejuni
ST464. Histochemistry of gut tissue demonstrated significant decreases in intestinal crypt depth in ileal tissue with increasing severity relative to
Campylobacter
lineage, M1 <ST353<ST464. Pairwise correlation analysis confirmed strong interdependencies between “cecal
Campylobacter
load,” “CXCLi1,” “CXCLi2,” and “splenic
Campylobacter
load.” Furthermore, linear discriminant analysis confirmed that cecal tonsil-derived IFNγ, TGFβ, and CXCLi1 could predict splenic invasion at 71% accuracy. This work demonstrates that two chicken specialist
C. jejuni
lineages, ST353 and ST464, cause extraintestinal spread to liver and spleen and modeling suggests distinct routes from ileum and cecum, respectively. Recognition of these two routes of
Campylobacter
extraintestinal spread (ileal/liver and cecal/spleen) provides a better understanding of this food-derived pathogen for academia and the industry.

IMPORTANCE

The UK is self-sufficient in chicken meat production, which remains a cheap and healthy source of dietary protein. However,
Campylobacter
species are present in 75% of raw chicken products at retail sales, resulting in increased human gut infections. Currently, it is not clear which members of the
Campylobacter jejuni
species can leave the digestive tract and reach edible tissues. Using industry-relevant conditions, two
C. jejuni
lineages (ST353 and ST464) isolated from chicken gut and liver were shown to cause infections outside the gut. The underlying mechanisms involve inducing inflammation and gut damage to structures required for cell renewal (crypts) of the intestine. Modeling this data leads to our proposal that
C. jejuni
uses two invasion pathways; one where spread is from ileum to liver and the other between ceca and spleen. Knowledge of these two routes of extraintestinal spread will help the industry develop control measures to improve food biosecurity in poultry.