Immunometabolic Phenotype Alterations Associated with the Induction of Disease Tolerance and Persistent Asymptomatic Infection of Salmonella in the Chicken Intestine

The adaptation of Salmonella enterica to the eukaryotic host is a key process that enables the bacterium to survive in a hostile environment. Salmonella have evolved an intimate relationship with its host that extends to their cellular and molecular levels. Colonization, invasion, and replication of the bacteria in an appropriate host suggest that modification of host functions is central to pathogenesis. Intuitively, this subversion of the cell must be a complex process, since hosts are not inherently programmed to provide an environment conducive to pathogens. Hosts have evolved countermeasures to pathogen invasion, establishment, and replication through two types of defenses: resistance and tolerance. Resistance functions to control pathogen invasion and reduce or eliminate the invading pathogen. Research has primarily concentrated on resistance mechanisms that are mediated by the immune system. On the other hand, tolerance is mediated by different mechanisms that limit the damage caused by a pathogen's growth without affecting or reducing pathogen numbers or loads. The mechanisms of tolerance appear to be separated into those that protect host tissues from the virulence factors of a pathogen and those that limit or reduce the damage caused by the host immune and inflammatory responses to the pathogen. Some pathogens, such as Salmonella, have evolved the capacity to survive the initial robust immune response and persist. The persistent phase of a Salmonella infection in the avian host usually involves a complex balance of protective immunity and immunopathology. Salmonella is able to stay in the avian ceca for months without triggering clinical signs. Chronic colonization of the intestinal tract is an important aspect of persistent Salmonella infection because it results in a silent propagation of bacteria in poultry stocks due to the impossibility to isolate contaminated animals. Data from our lab promote the hypothesis that Salmonella have evolved a unique survival strategy in poultry that minimizes host defenses (disease resistance) during the initial infection and then exploits and/or induces a dramatic immunometabolic reprogramming in the cecum that alters the host defense to disease tolerance. Unfortunately, this disease tolerance results in the ongoing human food safety dilemma.