e the capacity to shift from mutualist to commensal to parasite depending on the state of activation of the host, co-infection or localizations. Microbiota induces protective immune response by different mechanism to modulate the immune response. Firstly, they compete for nutrients, produce antimicrobial molecules and metabolites that affect the survival and virulence of pathogens. Furthermore, they also Promote the production of antimicrobial peptides by epithelial cells and reinforce tight junctions that directly affect pathogen growth or survival. In addition, microbiota also modulate the function of dendritic cells and other innate cells both locally and systemically so that it promotes the induction of effector T and B cells responses against pathogens.21
Mucosal firewall:
Microbiota minimize contact between microorganisms and the epithelial cell surface by maintaining homeostatic relationship with the host which further limits tissue inflammation and microbial translocation. This segregation is accomplished by the using epithelial cells, mucus, IgA, antimicrobial peptides and immune cells which are collectively known as “Mucosal firewall”.22 Each component of “mucosal firewall” performs different functions. Firstly, mucus acts as a primary barrier and it limits the contact between the microbiota and host tissue and thereby prevents microbial translocation.23 Epithelial cells also play an important role in limiting exposure to the commensal microbiota by producing antimicrobial peptides.24Tissue resident macrophages helps in eliminating translocating microbiota. Limitation of Microbiota is also done by CD103+ CD11b+DCs congesting to the mLN from the lamina propria but they do not penetrate deep and it leads to differentiation of commensal specific regulatory cells (Treg) Th17 cells and IgA producing B cells. Microbiota specific lymphocytes also traffic to Peyer’s Patches where Treg can further promote class switching and IgA generation against commensals.25
Formation of feedback loops:
Microbiota influence innate immunity by forming feedback loops. This loops are being regulated by various layers of intestinal wall and they perform three steps for stimulating innate immunity. Firstly, they recognize pattern recognition receptors like Toll-like receptors, the nucleotide-binding oligomerization like receptors, the RIG-I-like receptors, the C-type lectin receptors, the absent in melanoma 2 like receptors and the OAS like receptors. Then they mediate transcriptional response of the host; and, finally secrete effector molecules to mediate the immune response. The advantage of using such confined feedback loops is that the inflammatory response can be limited to the epithelial layer as they do not involve entire tissues or multiple organs. This loops involve communication between epithelial, myeloid and lymphoid cells using cytokines such as IL-18, IL-22, IL-23 and chemokines for mediating immune response.26
Transcriptional reprogramming:
Microbiota influence the activity of the innate immune system by transcriptional reprogramming. Transcriptional reprogramming involves expression of genes that are involves the host nutrient absorption and processing, barrier functions, gut motility, intestinal immune responses, angiogenesis and the metabolism of xenobiotics. Constituents of the microbiota have been involved in the regulation of ubiquitin signaling, protein neddylation, the nuclear translocation of transcription factor and vesicle trafficking.27Hooper et al, in their study found that reprogramming of intestinal gene expression was done by animals that were colonized with
