Cytokine and Chemokine Responses Associated with Clearance of a Primary Salmonella enterica Serovar Typhimurium Infection in the Chicken and in Protective Immunity to Rechallenge

Abstract

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 ␤4 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.

Immunological and gene expression responses to aSalmonellainfection in the chicken intestine

“…It was also shown that after infection with Salmonella the number of CD8 + TCRγδ + T-cells in the chicken intestine increased [6]. CD4 + or CD8 + T-cell responses are not required for the early host response [14], but CD4 + T-cell responses, particularly Th1 responses, play an important role in the clearance of Salmonella from the gastrointestinal tract [5,10,27].…”

Modulation of cytokine gene expression by selectedLactobacillusisolates in the ileum, caecal tonsils and spleen ofSalmonella-challenged broilers

“…LITAF is required throughout Salmonella infection. IL-12, secreted by activated macrophages, acts both independently and synergistically on natural killer cells and T helper (Th) cells to induce the production of further IFN-γ, which activates the macrophages through a positive feedback loop (Beal et al, 2004;Withanage et al, 2005;Haghighi et al, 2008;Tohidi et al, 2012). A correlation between cytokine profiles of chickens and their resistance to the infection by Salmonella Typhimurium was found (Mead, 2000).…”

“…Withanage et al (2005) reported that the expression of IL-6, well-known pro-inflammatory cytokine, was increased in the caecal tonsils, ileum, and spleen on day 1 p.i. and day 3 p.i.…”

“…Cytokine production can be modulated by commensal bacteria in the gastrointestinal tracts (Corthay, 2006). In chickens, pro-inflammatory, Th1, and Th2 cytokines have also been reported previously to contribute to the chicken immune response to Salmonella infection (Withanage et al, 2004(Withanage et al, , 2005. In these lines, in the present study, the expression of pro-inflammatory, Th1, and Th2 cytokines genes in response to Salmonella infection was evident, thus suggesting that both cellular and humoral immune responses have possibly been involved in the chicken defence.…”

Control of Salmonella in Poultry Through Vaccination and Prophylactic Antibody Treatment

“…The Guildhay method requires an initial serum dilution of 1:500 whereas similar work with killed Typhimurium used initial serum dilution of 1:250, 1:400 and 1:400 respectively Withanage et al, 2005;Bailey et al, 2007a). The higher initial dilution rate may have greatly reduced the number of ELISA positives in this trial.…”