Desired Turbulence? Gut-Lung Axis, Immunity, and Lung Cancer

Figure 1

Interaction of the microbiota and intestinal mucosa. (a) Microorganisms in the intestine provide pathogen-associated molecular patterns (PAMPs) that serve as ligands for different Toll-like receptors (TLRs) on the luminal or basolateral surface of the intestinal epithelial cells (IECs). (b) TLRs stimulation activates a signalling cascade resulting in transcription factor activation and gene transcription, enhancing the cell barrier and further stimulating the immunological cells in the lamina propria. This cascade can be inhibited by toll-interacting protein (TOLLIP). Inhibition seen only for TLR2 and TLR4 [23]. (c) Commensal bacteria and their derivatives (e.g., short-chain fatty acids (SCFAs)) directly stimulate IECs (b) or can be phagocytosed by DCs and macrophages in lamina propria and carried to mesenteric lymph nodes (MLN) where they prime naïve B and T cells to mature and differentiate. B cells become plasma cells and produce IgA that is secreted into the intestinal lumen (sIgA). T cells profile into Th17 and Th1, with proinflammatory tendency, activating additional effector cells as neutrophils, resulting in bacterial clearance. There is also differentiation to Treg cells having anti-inflammatory properties and controlling inflammation. APRIL: a proliferation-inducing ligand; BAFF: B cell-activating factor of the tumour necrosis family; DC: dendritic cell; IEC: intestinal epithelial cells; IFN: interferon; IL: interleukin; iNOS: inducible nitric oxide synthase; IRAK: interleukin receptor-associated kinase; JNK: c-Jun N-terminal kinases; LLN: lung lymph node; LPS: lipopolysaccharide; M: macrophage; MDPs: microbiota derived particles; MKK: mitogen-activated protein kinase kinase; MLN: mesenteric lymph node; MyD88: myeloid differentiation primary response gene 88; N: neutrophil; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; NK: natural killer cell; NOD: nucleotide-binding receptor; PAMPs: pathogen-associated molecular patterns; SCFAs: short-chain fatty acids; TAK-1: transforming growth factor beta-activated kinase; TGFβ: transforming growth factor beta; Th: T-helper cell; TLR: toll-like receptor; TNFα: tumour necrosis factor alfa; TOLLIP: toll-interacting protein; TRAF6: TNF receptor-associated factor 6; Treg: regulatory T cell.