Abstract
Salmonella enterica serovar Typhi (S. Typhi) porins, OmpC and OmpF, are potent inducers of the immune response against S. Typhi in mice and humans. Vaccination with porins induces the protection against 500 LD50 of S. Typhi, life-lasting bactericidal antibodies and effector T cell responses in mice; however, the nature of the memory T cell compartment and its contribution to protection remains unknown. In this work, we firstly observed that vaccination with porins induces in situ (skin) CD4+ and CD8+ T cell responses. Analysis of the porin-specific functional responses of skin CD4+ and CD8+ T cells showed IFN-gamma- and IL-17-producing cells in both T cell populations. The memory phenotype of porin-specific T cells indicated the presence of resident and effector memory phenotypes in the skin, and a central memory phenotype in the skin-draining lymph node. In addition, we demonstrated that vaccination with porins via skin reduces the bacterial burden following challenge. Finally, evaluating the role of the circulating T cell memory population in protection, we showed that circulating memory CD4+ and CD8+ T cells are crucial in porin-mediated protection against S. Typhi. Overall, this study highlights the importance of inducing circulating memory T cell responses in order to achieve the optimal protection provided by porins, showing a mechanism that could be sought in the rational development of vaccines.
Highlights
Salmonella enterica (S. enterica) is a human bacterial pathogen that represents a serious public health problem in low- and middle-income countries
In order to test whether vaccination with porins could induce T cell responses that would allow us to search different memory T cell subsets, we immunized mice using a prime-boost strategy followed by a delayed-type hypersensitivity (DTH) test
To evidence the presence of a local cellular response against porins, Delayed-Type Hypersensivity (DTH) tests were carried out in a group of mice that were primed and boosted with porins intradermally (PorID). Another group was primed with porins intraperitoneally (PorIP) and boosted with PorID, where a positive dermal DTH response would indicate that the priming with
Summary
Salmonella enterica (S. enterica) is a human bacterial pathogen that represents a serious public health problem in low- and middle-income countries. The World Health Organization has declared S. enterica as a high priority pathogen for the development of new antibiotics and vaccines due to the emergence of multi-drug resistant strains [1]. Typhi) is the cause of typhoid fever, of which approximately 11 million cases and 117,000 deaths are reported annually [2]. Vaccine development against S. enterica continues to be a challenge; only three vaccines against typhoid fever are currently licensed, some of them have limitations of effectiveness in young children, and none of them are able to provide cross-protection against non-typhoidal strains, which cause more than 93 million infections annually [3].
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