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Jay A. Fishman, Editorial Commentary: Immune Reconstitution Syndrome: How Do We “Tolerate” Our Microbiome?, Clinical Infectious Diseases, Volume 60, Issue 1, 1 January 2015, Pages 45–47, https://doi.org/10.1093/cid/ciu717
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(See the Major Article by Sun et al on pages 36–44.)
In the neonate, the immune system emerges in concert with commensal flora of the gastrointestinal (GI) tract, skin, and other sites. Interactions of the immune system with the human microbiome are required in development and maintenance of regulatory pathways that generate “tolerance” of innocuous organisms while allowing protective immune responses to invading pathogens. In the tolerogenic environment of the neonate, proinflammatory cytokine responses are blunted, and regulatory T lymphocytes (Tregs) emerge to suppress detrimental inflammatory responses. The microbiome shapes evolving lymphoid structures and intestinal mucosal barriers and limits development of autoimmune diseases. Tolerance to commensal organisms is controlled by CD4+/CD25+ Tregs from the thymus or induced in the GI tract [1–3]. The forkhead transcription factor Foxp3 is a marker for Tregs [4]. These cells function in part by production of interleukin 10 and by restriction of proinflammatory/cytotoxic T-helper 17 (Th17) lymphocyte responses [5]. The absence of this population of cells increases immune responses to alloantigens, contributing to rejection of allografts, inflammation, and development of autoimmune diseases [6]. Tregs may also attenuate immune responses to microbes [6]. In each tissue, a balance exists that protects against invasive infection while avoiding serious injury [7]. Specific microbes elicit an overt inflammatory response with tissue injury when a specific site of infection suffers from an inadequate host regulatory response. Thus, infection of the neuraxis couples limited space and poor regenerative capacity, predisposing to symptomatic infection.
