Innate Lymphoid Cells: Important Regulators of Host–Bacteria Interaction for Border Defense

Abstract

Innate lymphoid cells (ILCs) are a recently discovered type of innate immune lymphocyte. They include three different groups classified by the nature of the transcription factors required for their development and by the cytokines they produce. ILCs mainly reside in tissues close to the mucosal barrier such as the respiratory and gastrointestinal tracts. Due to their close proximity to the mucosal surface, ILCs are exposed to a variety of both commensal and pathogenic bacteria. Under non-pathological conditions, ILCs have been shown to be important regulators for the maintenance of tissue homeostasis by mutual interactions with the microbiome. Besides these important functions at homeostasis, several studies have also provided emerging evidence that ILCs contribute to defense against pathogenic bacterial infection by responding rapidly to the pathogens as well as orchestrating other immune cells. In this review, we summarize recent advances in our understanding of the interactions of ILCs and bacteria, with special focus on the function of the different ILC subsets in bacterial infections.

Cytokine-Mediated Crosstalk between Immune Cells and Epithelial Cells in the Gut

“…A recent interesting study linked IL-18 to the microbiota and the central nervous system by showing enteric neurons to be the major producers of this cytokine, other than IECs and immune cells [ 41 ]. Salmonella gastroenteritis infection results in the release of IL-1β and IL-12 that can induce ILC1s and B-cells to secrete high levels of IFN-γ and IgG antibodies, respectively [ 19 , 42 ]. Additionally, NCR3+ (natural cytotoxicity receptor) ILC3s have been shown to play a crucial role in both Salmonella and Listeria monocytogenes infections, in a Runt-related transcription factor 3 (Runx3)-dependent manner, modulating IFN-γ secretion [ 43 ].…”

“…DCs and T-cells can also sense Clostridium -derived metabolites, like short chain fatty acids (SCFA) and tryptophan, to induce proliferation of Tregs [ 44 ]. However in Rag1 −/− mice that lack T- and B lymphocytes, the ILC3s are the major responders during Clostridium infection, producing IL-22, IL-33, TNF, Nos2, IL-17a, and Reg3γ [ 42 ]. Indeed, ILCs and natural killer (NK) cells show high levels of plasticity when it comes to tackling certain bacterial infections like Citrobacter rodentium, a mouse-specific pathogen that mimics the disease symptoms caused by the human pathogens enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic Escherichia coli (EHEC).…”

Microbiome First Medicine in Health and Safety

“…In the gut, ILC- 1 cells control of Salmonella typhimurium in the gut, in the stomach, ILC-2 control Helicobacter pylori . In the lungs, the ILC-3 subpopulation controls Streptococcus pneumoniae [ 206 ]. While ILC-2 is a responder to Staphylococcus aureus in the skin [ 207 ].…”

Innate Lymphoid Cells and Natural Killer Cells in Bacterial Infections: Function, Dysregulation, and Therapeutic Targets

“…Besides NK cells, group 1 ILCs have shown to be central players in the protection against bacterial infections (Beck et al, 2020). ILC1s are potent producers of TNF-a and IFN-g upon stimulation with IL-12, IL-15 and IL-18, that allow them to play key roles in immune protection and chronic inflammation (Fuchs, 2016).…”

“…While ILC3s are important responders in the initial phase of C. rodentium infection, B lymphocytes and CD4 + T cells are crucial for resolution of C. rodentium infection (Simmons et al, 2003). In addition to activation of the surface receptors, various other mechanisms such as surrounding phagocytes, dietand bacteria-derived metabolites can contribute to ILC3 activation during C. rodentium infection (Beck et al, 2020). LTi-ILC3s are equipped with a wide variety of receptors, including MHCII, NK cell receptor P1 (NKR-P1R), G-protein-coupled receptors (GPCRs) (GPR183, free fatty acid receptor 2 (Ffar2)), aryl hydrocarbon receptor (AHR) that sense environmental cues to mount an appropriate response against C. rodentium when triggered by the pathogen (Lee et al, 2011;Chu et al, 2018;Li et al, 2018;Chun et al, 2019;Melo-Gonzalez et al, 2019).…”