Dietary Fiber Confers Protection against Flu by Shaping Ly6c− Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism

Abstract

Dietary fiber protects against chronic inflammatory diseases by dampening immune responses through short-chain fatty acids (SCFAs). Here we examined the effect of dietary fiber in viral infection, where the anti-inflammatory properties of SCFAs in principle could prevent protective immunity. Instead, we found that fermentable dietary fiber increased survival of influenza-infected mice through two complementary mechanisms. High-fiber diet (HFD)-fed mice exhibited altered bone marrow hematopoiesis, characterized by enhanced generation of Ly6c patrolling monocytes, which led to increased numbers of alternatively activated macrophages with a limited capacity to produce the chemokine CXCL1 in the airways. Blunted CXCL1 production reduced neutrophil recruitment to the airways, thus limiting tissue immunopathology during infection. In parallel, diet-derived SCFAs boosted CD8 T cell effector function by enhancing cellular metabolism. Hence, dietary fermentable fiber and SCFAs set an immune equilibrium, balancing innate and adaptive immunity so as to promote the resolution of influenza infection while preventing immune-associated pathology.

A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity

“…This suggests a systemic anti-inflammatory effect of RS. Reduced inflammation could explain a restoration in bone marrow physiology reflected by normalization of blood disorders (anemia and leukocytosis), bone marrow cellular repletion, and restored granulocyte-monocyte and megakaryocyte-erythrocyte progenitors populations (Figures S6D-S6F) (Soehnlein et al, 2017; Trompette et al, 2018; Ueda et al, 2005). Importantly, RS also significantly reduced renal immune infiltration and glomerulonephritis as well as proteinuria levels in TLR7.1 Tg mice (Figures 6G-6I).…”

‘Layered immunity’ and the ‘neonatal window of opportunity’ – timed succession of non‐redundant phases to establish mucosal host–microbial homeostasis after birth

“…Importantly, the underlying molecular mechanism of the protective effect of the microbiota is incompletely understood. The delivery of microbial constituents derived from a particular group of bacteria for tolerance induction, the supply with metabolic immunomodulators and/or the immunostimulatory capacity of microbial constituents may critically contribute …”

The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases

“…Administration of microbes (using probiotics or faecal transfer), microbe components, or products favouring their growth (e.g., prebiotics) has been suggested to confer host protection through direct competition with the disease-causing microbes, enhancement of epithelial barrier functions, or immune modulation during respiratory diseases(Alexandre et al, 2014;Trompette et al, 2018). tuberculosis infection.…”