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

Clegg, Jonah; Soldaini, Elisabetta; Bagnoli, Fábio; McLoughlin, Rachel M.

doi:10.1016/j.it.2020.11.005

Cited by 17 publications

(13 citation statements)

References 103 publications

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“…The immune response of the skin to S. aureus has been intensively investigated in a number of elegant mouse studies (19). However, the anatomical and immunological differences between murine and human skin together with the different composition and exposure to skin microbiome limit the translational value of the results obtained in mice (29,59).…”

Section: Discussionmentioning

confidence: 99%

“…Most importantly, Tsrm cells contribute to localized protection against re-infection with cutaneous pathogens (4)(5)(6)(7)(8)(9). In addition, Trm cell development has been tracked in mice following vaccination and was positively correlated with vaccination efficacy (10)(11)(12)(13), making Trm cells a promising target for vaccination (14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

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Staphylococcus aureus-Specific Tissue-Resident Memory CD4+ T Cells Are Abundant in Healthy Human Skin

Hendriks

Mnich

Clemente³

et al. 2021

Front. Immunol.

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The skin is an immunocompetent tissue that harbors several kinds of immune cells and a plethora of commensal microbes constituting the skin microbiome. Staphylococcus aureus is a prominent skin pathogen that colonizes a large proportion of the human population. We currently have an incomplete understanding of the correlates of protection against S. aureus infection, however genetic and experimental evidence has shown that CD4+ T cells play a key role in orchestrating a protective anti-S. aureus immune response. A high S. aureus-specific memory CD4+ T cell response has been reported in the blood of healthy subjects. Since T cells are more abundant in the skin than in blood, we hypothesized that S. aureus-specific CD4+ T cells could be present in the skin of healthy individuals. Indeed, we observed proliferation of tissue-resident memory CD4+ T cells and production of IL-17A, IL-22, IFN-γ and TNF-β by cells isolated from abdominal skin explants in response to heat-killed S. aureus. Remarkably, these cytokines were produced also during an ex vivo epicutaneous S. aureus infection of human skin explants. These findings highlight the importance of tissue-resident memory CD4+ T cells present at barrier sites such as the skin, a primary entry site for S. aureus. Further phenotypical and functional characterization of these cells will ultimately aid in the development of novel vaccine strategies against this elusive pathogen.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Staphylococcus aureus-Specific Tissue-Resident Memory CD4+ T Cells Are Abundant in Healthy Human Skin

Hendriks

Mnich

Clemente³

et al. 2021

Front. Immunol.

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“…Recently, the presence of S. aureus -specific tissue-resident CD4 + T cells in the skin of healthy subjects has been shown using abdominal skin explants ( 134 ). The protective efficacy of this frontline adaptive immune response could be harnessed by future vaccination strategies ( 135 ).…”

Section: Models For the Study Of S Aureus Infectionsmentioning

confidence: 99%

Staphylococcus aureus Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies

Clegg

Soldaini²,

McLoughlin

et al. 2021

Front. Immunol.

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Staphylococcus aureus is one of the most important human pathogens worldwide. Its high antibiotic resistance profile reinforces the need for new interventions like vaccines in addition to new antibiotics. Vaccine development efforts against S. aureus have failed so far however, the findings from these human clinical and non-clinical studies provide potential insight for such failures. Currently, research is focusing on identifying novel vaccine formulations able to elicit potent humoral and cellular immune responses. Translational science studies are attempting to discover correlates of protection using animal models as well as in vitro and ex vivo models assessing efficacy of vaccine candidates. Several new vaccine candidates are being tested in human clinical trials in a variety of target populations. In addition to vaccines, bacteriophages, monoclonal antibodies, centyrins and new classes of antibiotics are being developed. Some of these have been tested in humans with encouraging results. The complexity of the diseases and the range of the target populations affected by this pathogen will require a multipronged approach using different interventions, which will be discussed in this review.

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“…It is also possible that skin-resident T RM generated through intradermal vaccination may enhance both local and systemic host responses to Staphylococcus aureus, a common commensal of the skin and nasal mucosa, to help minimise Staphylococcal pneumonia (80).…”

Section: Vaccination Strategies To Promote T Rmmentioning

confidence: 99%

Pulmonary-Resident Memory Lymphocytes: Pivotal Orchestrators of Local Immunity Against Respiratory Infections

et al. 2021

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There is increasing evidence that lung-resident memory T and B cells play a critical role in protecting against respiratory reinfection. With a unique transcriptional and phenotypic profile, resident memory lymphocytes are maintained in a quiescent state, constantly surveying the lung for microbial intruders. Upon reactivation with cognate antigen, these cells provide rapid effector function to enhance immunity and prevent infection. Immunization strategies designed to induce their formation, alongside novel techniques enabling their detection, have the potential to accelerate and transform vaccine development. Despite most data originating from murine studies, this review will discuss recent insights into the generation, maintenance and characterisation of pulmonary resident memory lymphocytes in the context of respiratory infection and vaccination using recent findings from human and non-human primate studies.

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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.

Cited by 17 publications

References 103 publications

Staphylococcus aureus-Specific Tissue-Resident Memory CD4+ T Cells Are Abundant in Healthy Human Skin

Staphylococcus aureus-Specific Tissue-Resident Memory CD4+ T Cells Are Abundant in Healthy Human Skin

Staphylococcus aureus Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies

Pulmonary-Resident Memory Lymphocytes: Pivotal Orchestrators of Local Immunity Against Respiratory Infections

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