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Trained immunity is the capacity of innate immune cells to produce an improved response against a secondary infection after a previous unrelated infection or vaccination. Salmonellosis is a zoonosis, representing a threat to public health, and it also takes a toll on the pig farming industry. In general, the vaccination against salmonellosis is still facing problems regarding the control of distinct serovars. Therefore, we hypothesized that an immunostimulant based on heat inactivated Mycobacterium bovis (HIMB) could have an immune training effect in pigs challenged with Salmonella enterica serovar Choleraesuis (S. Choleraesuis), and decided to explore the amplitude of this non-specific immunological training.
Methods: For this purpose, twenty-four 10 days old female piglets were randomly separated in three groups: immunized group (n=10) received orally two doses of HIMB prior to the intratracheal S. Choleraesuis-challenge, positive control group (n=9) that was only challenged with S. Choleraesuis, and negative control group (n=5) that was neither immunostimulated nor infected. All individuals were necropsied 21 days post-challenge. Ante-mortem parameters analysed were: clinical signs, body temperature, weight and faecal shedding; while post-mortem parameters analysed were: bacterial tissue colonization, pulmonary lesions and cytokines expression.
Results: Results showed that immune response training with HIMB was effective in reducing clinical signs and limiting temperature rise and weight loss. Moreover, the HIMB group displayed significantly lower pulmonary pathology scores, improving animal health status. However, S. Choleraesuis excretion and tissue colonization were not reduced by HIMB immunostimulant. The principal immunological mechanism involved in the decrease of lung lesions associated to HIMB immunostimulation was the overexpression of CCL28, signalling the importance of innate immunity in the non specific protection against S. Choleraesuis.
Conclusion: This proof-of-concept study suggests beneficial clinical, pathological and immunological effects against heterologous bacterial pathogens within the concept of trained immunity, opening avenues for further research.
