Immunity to intestinal pathogens: lessons learned from Salmonella

Abstract

Summary Salmonella are a common source of food or water-borne infection and cause a wide range of clinical disease in human and animal hosts. Salmonella are relatively easy to culture and manipulate in a laboratory setting, and the infection of laboratory animals induces robust innate and adaptive immune responses. Thus, immunologists have frequently turned to Salmonella infection models to expand understanding of immunity to intestinal pathogens. In this review, I summarize current knowledge of innate and adaptive immunity to Salmonella and highlight features of this response that have emerged from recent studies. These include the heterogeneity of the antigen-specific T-cell response to intestinal infection, the prominence of microbial mechanisms to impede T and B-cell responses, and the contribution of non-cognate pathways for elicitation of T-cell effector functions. Together, these different issues challenge an overly simplistic view of host-pathogen interaction during mucosal infection but also allow deeper insight into the real-world dynamic of protective immunity to intestinal pathogens.

Evaluation of the effectiveness and safety of a genetically modified live vaccine in broilers challenged with Salmonella Heidelberg

“…Both the innate immune system and the specific immunity conferred by vaccination with live vaccine help prevent intestinal colonization, and the later the challenge takes place, the greater the effectiveness of the vaccination programme (McSorley, 2014). Although the differences in prevalences between the vaccinated and control groups were not statistically significant, there was a reduction in the percentage of positive liver/spleen results in birds inoculated at 21 days of age, indicating a beneficial trend from the use of the vaccine to reduce visceral contamination (Table 4).…”

Salmonella infection: Interplay between the bacteria and host immune system

“…Generally, CD8 T cells are not thought to contribute to the primary clearance of Salmonella [86] and depletion of CD8 T cells during the persistent stages of infection does not lead to increased bacterial burdens in systemic organs [87,88]. Conversely, studies using β2M-deficient mice lacking surface MHC Class I expression demonstrate these mice are capable of resolving infection with attenuated Salmonella [89], however, these mice are also deficient in the expression of non-classical MHC molecules and CD1, confounding the interpretation of the role of MHC Class I restricted antigens in protective Salmonella immune responses [90].…”

Salmonella Infection Enhances Erythropoietin Production by the Kidney and Liver, Which Correlates with Elevated Bacterial Burdens

“…Thus, the development of new vaccines for typhoid and nontyphoidal salmonellosis (NTS) is an important public health priority. However, the generation of effective vaccines will require a greater understanding of how the innate and adaptive immune responses recognize and combat Salmonella infections (11).…”

“…Although Salmonella enterica serovar Typhimurium causes gastroenteritis in humans, it causes a disseminated infection in mice that displays some similarities to human typhoid and NTS (12,13). This murine infection has been widely used as a model to understand Salmonella pathogenesis and the host immune response to infection (11,14). Salmonella immunity in mice requires the coordinated activation of innate and adaptive immune compartments, leading to a wide variety of immune effector mechanisms that eliminate bacteria and establish protective immunity to secondary challenge (11,15).…”

“…This murine infection has been widely used as a model to understand Salmonella pathogenesis and the host immune response to infection (11,14). Salmonella immunity in mice requires the coordinated activation of innate and adaptive immune compartments, leading to a wide variety of immune effector mechanisms that eliminate bacteria and establish protective immunity to secondary challenge (11,15). Both CD4 and CD8 T cells contribute to the resolution of primary Salmonella infection, while CD4 T cells play a dominant role in providing secondary protective immunity (16)(17)(18).…”