Commensal Bacteria Calibrate the Activation Threshold of Innate Antiviral Immunity

By Michael C. Abt, L. Osborne, L. Monticelli, Travis A. Doering, T. Alenghat, Gregory F. Sonnenberg, Michael A. Paley, Marcelo Antenus, Katie L. Williams, J. Erikson and 2 more. Immunity, 2012

957 citations recorded by the source corpus.

SUMMARY Signals from commensal bacteria can influence immune cell development and susceptibility to infectious or inflammatory diseases. However, the mechanisms by which commensal bacteria regulate protective immunity after exposure to systemic pathogens remain poorly understood. Here, we demonstrate that antibiotic-treated (ABX) mice exhibit impaired innate and adaptive antiviral immune responses and substantially delayed viral clearance after exposure to systemic LCMV or mucosal influenza virus. Furthermore, ABX mice exhibited severe bronchiole epithelial degeneration and increased host mortality after influenza virus infection. Genome-wide transcriptional profiling of macrophages isolated from ABX mice revealed decreased expression of genes associated with antiviral immunity. Moreover, macrophages from ABX mice exhibited defective responses to type I and type II IFNs and impaired capacity to limit viral replication. Collectively, these data indicate that commensal-derived signals provide tonic immune stimulation that establishes the activation threshold of the innate immune system required for optimal antiviral immunity.

Subfields: Epidemiology, Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/68333520cd873d65bba1f1aa60b5f6e19072723b

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In Epidemiology

1. Eric G. Pamer
2. Y. Belkaid
3. T. Hand

In Immunology

1. Y. Belkaid
2. Eric G. Pamer
3. J. Wargo
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In Molecular Biology

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Citations in the corpus

• Wild Mouse Gut Microbiota Promotes Host Fitness and Improves Disease Resistance (2017, neutral): “It is well known that the bacterial gut microbiome affects disease outcomes in influenza virus infection (Abt et al., 2012; Ichinohe et al., 2011; Oh et al., 2014) and colorectal tumorigenesis models (Zackular et al., 2013, 2016).”
• The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy. (2018, background): “…transcriptional level) to enact a robust response in the setting of pathogens, and, in the absence of threat, to maintain a non-inflammatory state (Abt et al., 2012) Furthermore, B and T cells, including Tregs and Th17 cells, can, upon being primed by DCs presenting antigen derived from commensal…”
• Bifidobacteria-mediated immune system imprinting early in life (2020, neutral): “Also, other studies have described a role for microbiota-induced IFNb in determining immune responses to viral challenges (Abt et al., 2012; Schaupp et al., 2020).”
• Homeostatic immunity and the microbiota (2017, neutral): “Antibiotic treatment also impaired adaptive and innate responses following exposure to systemic viral infections (Abt et al., 2012).”
• Role of the Microbiota in Immunity and inflammation (2014, background): “Genome-wide transcriptional profiling of macrophages from antibiotic-treated mice revealed a broad decrease of genes associated with antiviral immunity (Abt et al., 2012).”
• Antibiotic-Induced Changes in the Intestinal Microbiota and Disease. (2016, background): “Antibiotics have been shown to impair immunity against lymphocytic choriomeningitis virus (LCMV) in mice by lowering the expression of antiviral genes such as Ifnb and Irf7 in lung macrophages, resulting in defects in CD8 T cell expansion, as well as in IFN-g/TNF-/ and IgG production [26].”