Table 1.
A summary of the main function of different innate immune subsets and their phenotypes related to microbiota alterations.
| Cell type | Subset | Main function | Phenotype related to microbiota alterations | References |
|---|---|---|---|---|
| ILC | cNK cells | Anti-virus Anti-tumor Cytotoxicity: perforin, granzyme, TRAIL, ADCC Cytokine: TNF, IFN-γ, and GM-CSF |
Decreased cytotoxicity and cytokine production in GF mice Microbiota primes cNK cells via dendritic cells epigenetically |
(93) (94) |
| ILC1 | Anti-virus Anti-tumor Cytokine: TNF and IFN-γ |
Low frequency of ILC1 in fetal gut Increased ILC3-related elements upon microbiota depletion |
(68, 113) (116) |
|
| ILC2 | Anti-parasite Wound healing Cytokine: IL-13 and IL-5 |
Activated by IL-25, IL-33, and TSLP produced by intestinal epithelium in response to commensals Butyrate suppress IL-5/IL-13 production by ILC2 via HDAC inhibition |
(114) (115) |
|
| ILC3 | Intestinal barrier Anti-virus Anti-bacteria Cytokine: IL-17 and IL-22 |
Differentiation and IL-22 production are microbiota-dependent Microbiota inhibit IL-22 production by ILC3 ID2-deficiency downregulate IL-22 production of ILC3, resulting in dysbiosis ILC3 process antigens from symbiotic bacteria and restrain self-reactive T cells Microbiota induce IL-22 production of ILC3 to enhance intestinal barrier |
(97) (100) (103) (109, 110) (108) |
|
| LTi cells | Induction of secondary lymphoid tissue formation Cytokine: IL-17 and IL-22 | Peptidoglycan from Gram-negative bacteria activate LTi enriched in cryptopatches |
(49) | |
| Phagocytes | Macrophages | Phagocytosis Antigen presentation M1 macrophage: pro-inflammatory, anti-bacteria M2 macrophage: wound healing, tissue repair, IL-10 production |
Microbiota induce CCR2 expression for macrophage homing Microbiota promote myelopoiesis Microbiota drive the expression of HDAC3 to promote IL-10 production SCFAs downregulate pro-inflammatory cytokine in a HDAC-dependent manner |
(118) (119) (128) (129) |
| Dendritic cells | Antigen presentation Phagocytosis |
Dysbiosis cause CD103+ DC accumulation in epithelium In colitis CX3CR1+ DC migrate to mLNs to present antigens Microbiota induce trimethylation of H3K4 to induce IL-6 and IFNβ1 secretion |
(124) (120, 125) (94) |