CD4+ and CD8+ Circulating Memory T Cells Are Crucial in the Protection Induced by Vaccination with Salmonella Typhi Porins

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.

Intranasal immunization of mice with chimera of Salmonella Typhi protein elicits protective intestinal immunity

“…In contrast, CD8 + T cells were predominantly polyfunctional, 80% of which showed T EM phenotype and produced triple cytokines 56 . The requirement of circulating memory CD4 + and CD8 + T cells as well as TNF-α and IFN-γ for protection against Salmonella was shown in mice after oral immunization with aroA-attenuated live vaccine strain or intradermal immunization with porins 57 , 58 . Here, we show that mice that received intranasal CTB as a chimeric partner augmented T2544-specific memory CD4 + response, which upregulated IFN-γ production and were constituted by equal numbers of T EM and T CM (Fig.…”

Intranasal Immunization of Mice with a Chimeric Antigen of Cholera Toxin B and Salmonella Typhi outer membrane protein T2544 elicits protective antibodies and T cell response at the intestinal mucosa

“…Oral vaccination of volunteers with Ty21a generated largely monofunctional CD4 + T EM or T EMRA cells that produced high levels of IL-17A or TNF-α, as opposed to polyfunctional CD8 + cells, 80% of which showed T EM phenotype and produced triple cytokines 51 . The requirement of circulating memory CD4 + and CD8 + T cells as well as TNF-α and IFN-γ for protection against Salmonella was shown in mice by oral immunization with aroA-attenuated live vaccine strain or intradermal immunization with porins 52,53 . We had previously reported induction of S. Typhi-speci c CD4 + T cells, producing high levels of IFN-γ in mice after subcutaneous immunization with rT2544 9 .…”

Protease shaving ofMycobacterium tuberculosisfacilitates vaccine antigen discovery and delivery of novel cargoes to the Mtb surface

“…In gram-negative bacteria there is a subset of highly conserved outer membrane proteins called porins which play a role in small molecule transport across the membrane and bacterial homeostasis. OmpC and OmpF in Salmonella enterica serovar Typhi both induce a robust cell-mediated immune response in mice and humans 17 .…”