Editorial: How Salmonella Infection can Inform on Mechanisms of Immune Function and Homeostasis

Our ability to survive requires the competency to control infection. In the last 50 years, there has been an explosion in our understanding of the processes that underlie this. Central to this is our ability to restrict the infection to local sites and so prevent it from becoming systemic. Infections caused by serovars of the species Salmonella enterica, spread through fecal–oral transmission, exemplify this and are a major reason why this organism was chosen as the theme of this Research Topic. Salmonella infections, particularly typhoidal infections, have had their hand on the tiller of human history, able to steer fate in new directions as a consequence of their deadly properties. A key element of this is the ability to spread through the host and this is often associated with the capacity to cause fatal infections. The prevention of infection and the control of bacterial spread require the complex interplay between themicrobiota and innate and adaptive immunemechanisms. The effects of Salmonella infections on the complex systems that regulate their control can leave shortand long-term footprints on the homeostatic functions of the host, for instance in the thymus and bone marrow (1, 2), broadens the significance of their study. The depth of interest in this organism is represented in this Research Topic. The reasons behind the diverse clinicalmanifestations of this infection are introduced byGal-Mor and colleagues (3), who discuss the differences between typhoidal and non-typhoidal Salmonella strains. This overview includes introducing antigens, including Vi capsule, which can be differentially expressed, as well as the distinct immune responses induced by different serovars. Whilst most groups focus their studies on Salmonella infections in mammalian hosts, it should be remembered that many serovars can colonize other organisms too, and indeed this provides a reservoir for most non-typhoidal strains.Wigley highlights the importance of Salmonella infection in chickens, both as a source of zoonotic infection, but also as a disease in itself and one of major economic importance (4). Furthermore, we can learn so much from this system, for instance chickens lack lymph nodes, have different MHC and TLR usage, and lack IgG subclasses, so the regulation of the immune response is likely to have multiple unique features. Although the severity of Salmonella infections in humans and mice is associated with its systemic spread, there is obviously a close relationship with the gut, well described as “a mucosal pathogen with a systemic agenda” (5). In immunological terms, this is a fascinating relationship to study. Inmanyways, a primary aimof themucosal system is to limit inflammation to maintain barrier integrity, whereas systemic immunity often dramatically exploits inflammation to contain infection. This is neatly exploited by non-typhoidal Salmonella strains that are commonly associated with gastrointestinal infection and inflammation. In addition, Vi-expressing S. Typhi may also exploit lower levels of mucosal inflammation to help it spread throughout the host (6). Several works in this edition refer to relationship between the pathogen and the gut. Santos examines the three-way relationship between Salmonella, the microbiota, and the innate immune system, with a particular emphasis on how the microbiota can buffer against infection (7). Patel and McCormick further develop this concept to encompass details on the ability of Salmonella to exploit innate barriers and immune cells via type III secretion systems to establish