Virulence factors of Salmonella Typhi: interplay between the bacteria and host macrophages

Salmonella Typhi (S. Typhi) is a Gram-negative bacterium that exclusively infects humans and causes typhoid fever– a major global public health concern responsible for approximately 9 million infections and 110,000 deaths annually. Macrophages, a key component of the innate immune system, play essential roles in pathogen clearance, antigen presentation, immune regulation, and tissue repair. As one of the primary targets of S. Typhi infection, macrophages significantly influence disease onset and progression. S. Typhi expresses a range of virulence factors, including the virulence-associated (Vi) capsule, outer membrane proteins (OMPs), flagella, fimbriae, type III secretion systems (T3SSs) and other genes encoded on Salmonella pathogenicity islands (SPIs), as well as toxins, regulatory factors, and virulence plasmids. These virulence factors facilitate S. Typhi’s intracellular survival within macrophages by mediating processes such as adhesion, invasion, nutrient acquisition and immune evasion, ultimately enabling systemic infection. This review explores the role and molecular mechanisms of S. Typhi virulence factors in counteracting macrophage antimicrobial functions, providing insights for future research on typhoid pathogenesis and the development of potential therapeutic interventions.