Infection of poultry with Salmonella enterica serovar Typhimurium poses a significant risk to public health through contamination of meat from infected animals. Vaccination has been proposed to control
infections in chickens. However, the
vaccines are currently largely empirical, and our understanding of the mechanisms that underpin immune clearance and protection in avian
salmonellosis is not complete. In this study we describe the
cytokine,
chemokine, and antibody responses and cellular changes in primary and
secondary infections of chickens with Salmonella serovar Typhimurium.
Infection of 1-week-old chickens induced early expression of a
macrophage inflammatory protein (MIP) family
chemokine in the spleen and liver, followed by increased expression of
gamma interferon accompanied by increased numbers of both CD4(+) and CD8(+) T cells and the formation of
granuloma-like follicular lesions. This response correlated with a Th1-mediated clearance of the systemic
infection. Primary
infection also induced specific
immunoglobulin M (
IgM),
IgG, and
IgA antibody responses. In contrast to previously published studies performed with newly hatched chicks, the expression levels of proinflammatory
cytokines in the gastrointestinal tract were not greatly increased following
infection. However, significant expression of the anti-inflammatory
cytokine transforming growth factor beta4 was detected in the gut early in
infection. Following secondary challenge, the birds were fully protected against systemic
infection and showed a high level of protection against gastrointestinal colonization. Rapid expression of the MIP family
chemokine and
interleukin-6 was detected in the guts of these birds and was accompanied by an influx of lymphocytes. Increased levels of serum
IgA-specific
antibodies were also found following rechallenge. These findings suggest that cellular responses, particularly Th1 responses, play a crucial role in immune clearance in avian
salmonellosis and that protection against rechallenge involves the rapid recruitment of cells to the gastrointestinal tract. Additionally, the high levels of inflammatory response found following Salmonella serovar Typhimurium
infection of newly hatched chicks were not observed following
infection of older birds (1 week old), in which the expression of regulatory
cytokines appeared to limit
inflammation.