Targeting Skin-Resident Memory T Cells via Vaccination to Combat Staphylococcus aureus Infections

Abstract

Mammalian tissue-resident memory T cells are a relatively recently identified population added to the arsenal of adaptive immune cells. These cells are thoroughly being investigated in the study of many tissue-specific diseases.Novel vaccination strategies and biotechnological devices are facilitating the harnessing and sampling of tissue-specific immunity in the skin. In addition, the dynamics of skin-wide immunosurveillance are beginning to be understood.While the importance of T cell immunity during Staphylococcus aureus skin and soft-tissue infections is established, determining the correlates of immunity to develop candidate vaccines remains elusive.Skin-resident memory T cells are a possible missing piece in the immunity puzzle of S. aureus infections. Targeting this population may prove to be significant for the development of a putative successful vaccine against skin and soft tissue S. aureus infections. Tissue-resident memory T cells are important in adaptive immunity against many infections, rendering these cells attractive potential targets in vaccine development. Genetic and experimental evidence highlights the importance of cellular immunity in protection from Staphylococcus aureus skin infections, yet skin-resident memory T cells are, thus far, an untested component of immunity during such infections. Novel methods of generating and sampling vaccine-induced skin memory T cells are paralleled by discoveries of global, skin-wide immunosurveillance. We propose skin-resident memory CD4+ T cells as a potential missing link in the search for correlates of protection during S. aureus infections. A better appreciation of their phenotypes and functions could accelerate the development of preventive vaccines against this highly virulent and antibiotic-resistant pathogen. Tissue-resident memory T cells are important in adaptive immunity against many infections, rendering these cells attractive potential targets in vaccine development. Genetic and experimental evidence highlights the importance of cellular immunity in protection from Staphylococcus aureus skin infections, yet skin-resident memory T cells are, thus far, an untested component of immunity during such infections. Novel methods of generating and sampling vaccine-induced skin memory T cells are paralleled by discoveries of global, skin-wide immunosurveillance. We propose skin-resident memory CD4+ T cells as a potential missing link in the search for correlates of protection during S. aureus infections. A better appreciation of their phenotypes and functions could accelerate the development of preventive vaccines against this highly virulent and antibiotic-resistant pathogen. Infection leads to the clonal expansion (see Glossary) of long-lived memory lymphocytes that mediate adaptive immunity. It was typically understood that these memory cell populations exist in the bloodstream and lymphoid organs in which they constantly recirculate, awaiting reactivation, and with limited entry into peripheral tissues. However, in recent years, numerous studies have showcased the existence and importance of a tissue-resident memory T cell (Trm) population during states of infection, cancer, and homeostasis in mammalian hosts. Trm are identified by their disequilibrium with the circulatory system, which distinguishes them from other characterized memory T cell populations, namely, central memory T cells (Tcm) and effector memory T cells (Tem) (Figure 1). In addition to this functional distinction, Trm have also been transcriptionally defined in mice (Box 1) [1.Kumar B.V. et al.Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites.Cell Rep. 2017; 20: 2921-2934Abstract et immune by memory T Trm many in the they as of the adaptive immune and to of Trm have been in of with and in many peripheral the skin 1). Trm may an vaccine against infections. vaccination strategies have been in mice to Trm organs such as the and expansion of tissue-resident T cells to cellular immunity in the Rep. 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