Historical Aspects of Mucosal Immunology

Městecký, Jiří

doi:10.1016/b978-0-12-415847-4.02001-2

Cited by 6 publications

(4 citation statements)

References 228 publications

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“…Evidence for the intestine as a primary lymphoid organ was first demonstrated in birds which have the bursa of Fabricus in the cloaca (equivalent to rectum), which is responsible for their generation of B cells (reviewed in [163]. Similarities between the sacculus rotundus of rabbits and the bursa of birds originally prompted some to consider this massive B cell rich region of the rabbit intestine to be a primary lymphoid organ as well [163, 164]. More recently however, and with new technologies, the concept that GALT may contain primary lymphoid tissues capable of replenishing B cell follicles and possibly T cells is re-emerging.…”

Section: Intestinal Cd4+ T Cell Reconstitution After Hiv Infectionmentioning

confidence: 99%

Intestinal CD4 Depletion in HIV / SIV Infection

Veazey

2019

CIR

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Among the most significant findings in the pathogenesis of HIV infection was the discovery that almost total depletion of intestinal CD4+ T cells occurs rapidly after SIV or HIV infection, regardless of the route of exposure, and long before CD4+ T cell losses occur in blood or lymph nodes. Since these seminal discoveries, we have learned much about mucosal and systemic CD4+ T cells, and found several key differences between the circulating and intestinal CD4+ T cell subsets, both in phenotype, relative proportions, and functional capabilities. Further, specific subsets of CD4+ T cells are selectively targeted and eliminated first, especially cells critically important for initiating primary immune responses, and for maintenance of mucosal integrity (Th1, Th17, and Th22 cells). This simultaneously results in loss of innate immune responses, and loss of mucosal integrity, resulting in mucosal, and systemic immune activation that drives proliferation and activation of new target cells throughout the course of infection. The propensity for the SIV/HIV to infect and efficiently replicate in specific cells also permits viral persistence, as the mucosal and systemic activation that ensues continues to damage mucosal barriers, resulting in continued influx of target cells to maintain viral replication. Finally, infection and elimination of recently activated and proliferating CD4+ T cells, and infection and dysregulation of Tfh and other key CD4+ T cell results in hyperactive, yet non-protective immune responses that support active viral replication and evolution, and thus persistence in host tissue reservoirs, all of which continue to challenge our efforts to design effective vaccine or cure strategies.

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Section: Intestinal Cd4+ T Cell Reconstitution After Hiv Infectionmentioning

confidence: 99%

Intestinal CD4 Depletion in HIV / SIV Infection

Veazey

2019

CIR

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“…Reciprocal interactions between host and microbiota contribute to tissue function and homeostasis and determine microbiota composition, thereby playing an important role in infection and disease (87). For example, members of the intestinal microbiota regulate production of antimicrobial peptides by Paneth cells (88) and shape immune responses by regulating numbers, subsets, and/or functions of T, B, and myeloid cells (65). Microbiota-induced changes in immunity also determine intestinal microbiota composition (85,89).…”

mentioning

confidence: 99%

“…Mucosal tissues contain an array of small molecules, including innate defense mediators that target pathogens and regulate downstream host defenses. Intestinal mucus harbors compounds from the innate and adaptive systems that protect against microbial insult, including digestive enzymes (e.g., lysozyme), lactoferrin, antimicrobial peptides, complement, and antibodies (e.g., secretory immunoglobulin A [sIgA]) (65). In addition, cells of the innate defense system respond to pathogenassociated molecular patterns (PAMPs) using pathogen recognition receptors (PRRs).…”

mentioning

confidence: 99%

“…Depending on the pathogen, PRR-mediated signal transduction results in different cellular outcomes (e.g., cell proliferation, apoptosis, antimicrobial peptide production, autophagy, and cytokine secretion). Cytokine production leads to recruitment of innate and adaptive immune effectors to the infection site, representing a bridge between these two arms of immunity (65,101).…”

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confidence: 99%

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Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age

et al. 2018

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Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g., fluid shear, stretch, compression). A major challenge in tissue engineering for infectious disease research is recreating this dynamic 3-D microenvironment (biological, chemical, and physical/mechanical) to more accurately model the initiation and progression of host-pathogen interactions in the laboratory. Here we review selected 3-D models of human intestinal mucosa, which represent a major portal of entry for infectious pathogens and an important niche for commensal microbiota. We highlight seminal studies that have used these models to interrogate host-pathogen interactions and infectious disease mechanisms, and we present this literature in the appropriate historical context. Models discussed include 3-D organotypic cultures engineered in the rotating wall vessel (RWV) bioreactor, extracellular matrix (ECM)-embedded/organoid models, and organ-on-a-chip (OAC) models. Collectively, these technologies provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies at the intersection of the host, microbe, and their local microenvironments.

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