Immunological, cellular and molecular events in typhoid fever

Salmonella, a facultative intracellular Gram-negative bacterium infects a wide range of hosts causing several gastrointestinal diseases and enteric fever in humans and certain animal species. Typhoid caused by Salmonella typhi remains a major health concern in India and worldwide. Also, with emergence of multidrug resistant strains, Salmonella has acquired increased virulence, communicability and survivability, resulting in increased morbidity and mortality. Though a number of vaccines for typhoid are available against S. typhi (or also against S. typhimurium), these have certain undesirable side effects and the search for new immunogens suitable for vaccine formulation is still continuing. The immune response to primary Salmonella infection involves both humoral and cell-mediated responses. The protective immunity against Salmonella depends on host- parasite interaction, however; the detailed mechanism of virulence, innate resistance and susceptibility of host remains unclear. This review focuses on the molecular, immunological and cellular mechanisms of pathogenesis of Salmonella infection to provide an insight to counteract bacterial infections and allow a better understanding of its clinical manifestations. It also reviews better technological possibilities combined with increased knowledge in related fields such as immunology and molecular biology and allow for new vaccination strategies. Some new approaches such as subunit and nucleic acid vaccines and recombinant antigen which are becoming increasingly important for the development of potential vaccines have also been discussed. A significant progress has been made in our understanding of Salmonella pathogenesis. Despite these efforts, however, many challenges exist, especially for investigators who aim to understand how the pathogenic mechanisms operating in vitro apply to in vivo model systems. However, unyielding work and collaborations between Salmonella researchers and clinicians worldwide have made significant contributions to understanding the interaction between virulence determinants and immunity required to stop the spread of this pathogen.