Enhancing mucosal immunity by transient microbiota depletion

Becattini, Simone; Seok, Ruth; Amoretti, Luigi A.; Fontana, Emily; Wright, Roberta J.; Gjonbalaj, Mergim; Leiner, Ingrid; Plitas, George; Hohl, Tobias M.; Pamer, Eric G.

doi:10.1038/s41467-020-18248-4

Cited by 13 publications

(16 citation statements)

References 75 publications

(115 reference statements)

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“…Consistently, a recent study showed that an oral typhoid vaccine was able to induce antigen-specific CD4 + T RM cells in the human small intestine ( 46 ). Additionally, transient microbiota depletion-boosted immunization in mice has been proposed as a strategy to optimize T RM cell generation upon exposure with vaccine antigens ( 47 ).…”

Section: T Rm Cells In Intestinal Infection Contromentioning

confidence: 99%

Total Recall: Intestinal TRM Cells in Health and Disease

et al. 2021

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Tissue-resident memory T cells (TRM cells) have crucial functions in host defense in mucosal tissues. They provide local adaptive immune surveillance and allow the fast initiation of targeted adaptive immune responses in case of antigen re-exposure. Recently, an aberrant activation in the case of immunologically mediated diseases has been increasingly acknowledged. As the organ with the largest interface to the environment, the gastrointestinal tract faces billions of antigens every day. Tightly balanced processes are necessary to ensure tolerance towards non-hazardous antigens, but to set up a powerful immune response against potentially dangerous ones. In this complex nexus of immune cells and their mediators, TRM cells play a central role and have been shown to promote both physiological and pathological events. In this review, we will summarize the current knowledge on the homeostatic functions of TRM cells and delineate their implication in infection control in the gut. Moreover, we will outline their commitment in immune dysregulation in gastrointestinal chronic inflammatory conditions and shed light on TRM cells as current and potential future therapeutic targets.

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Section: T Rm Cells In Intestinal Infection Contromentioning

confidence: 99%

Total Recall: Intestinal TRM Cells in Health and Disease

et al. 2021

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“…While targeting specific bacterial competitors (present in the mouse microbiome, absent in the human microbiome) may generate more relevant mouse models to study L. monocytogenes infection, their protective potential when administered as probiotics in humans remains to be studied. Alternatively, transient depletion of mouse microbiota may favour intestinal exposure to engineered L. monocytogenes carrying a highly immunogenic antigen 89 . This approach to boost the immune response may be a useful platform to study vaccination at the intestinal mucosa in humans.…”

Section: Use Of In Vivo Infection Models For Human Health Impactmentioning

confidence: 99%

Emerging technologies and infection models in cellular microbiology

López-Jiménez

Mostowy

2021

Nat Commun

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The field of cellular microbiology, rooted in the co-evolution of microbes and their hosts, studies intracellular pathogens and their manipulation of host cell machinery. In this review, we highlight emerging technologies and infection models that recently promoted opportunities in cellular microbiology. We overview the explosion of microscopy techniques and how they reveal unprecedented detail at the host-pathogen interface. We discuss the incorporation of robotics and artificial intelligence to image-based screening modalities, biochemical mapping approaches, as well as dual RNA-sequencing techniques. Finally, we describe chips, organoids and animal models used to dissect biophysical and in vivo aspects of the infection process. As our knowledge of the infected cell improves, cellular microbiology holds great promise for development of anti-infective strategies with translational applications in human health.

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“…Extracellular ATP derived from intestinal microbiota, activated cells and/or damaged tissue restores TGF-βRII expression and TGF-β responsiveness, resulting in CD8 + T cell CD103 upregulation, KLF2 downregulation, enhanced mitochondrial function and T RM formation ( 125 ). On the other hand, microbiota depletion by antibiotic treatment increases the antigen load following LM infection and promotes CXCR3-directed CD8 + T cell accumulation within the large intestinal lamina propria, resulting in increased mucosal CD8 + T RM accumulation and response ( 126 ).…”

Section: Stage 2: Mechanisms That Encourage Cd8 + T Rm To Settle In Peripheral Tissuesmentioning

confidence: 99%

Discipline in Stages: Regulating CD8+ Resident Memory T Cells

Mora-Buch

Bromley

2021

Front. Immunol.

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Resident memory CD8+ T (TRM) cells are a lymphocyte lineage distinct from circulating memory CD8+ T cells. TRM lodge within peripheral tissues and secondary lymphoid organs where they provide rapid, local protection from pathogens and control tumor growth. However, dysregulation of CD8+ TRM formation and/or activation may contribute to the pathogenesis of autoimmune diseases. Intrinsic mechanisms, including transcriptional networks and inhibitory checkpoint receptors control TRM differentiation and response. Additionally, extrinsic stimuli such as cytokines, cognate antigen, fatty acids, and damage signals regulate TRM formation, maintenance, and expansion. In this review, we will summarize knowledge of CD8+ TRM generation and highlight mechanisms that regulate the persistence and responses of heterogeneous TRM populations in different tissues and distinct microenvironments.

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Enhancing mucosal immunity by transient microbiota depletion

Cited by 13 publications

References 75 publications

Total Recall: Intestinal TRM Cells in Health and Disease

Total Recall: Intestinal TRM Cells in Health and Disease

Emerging technologies and infection models in cellular microbiology

Discipline in Stages: Regulating CD8+ Resident Memory T Cells

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