The role of the immune system in regulating the microbiota

Figures & data

Figure 1 Disrupting microbial function. (A) In a healthy gut bacteria work synergistically, with each bacteria being an integral link in the production of metabolites that are ultimately used by the host, such as vitamins and fatty acids. (B) Host inflammation targets certain groups of bacteria resulting in a loss of core members and core functions, therefore reduced metabolic activity and a deprived host.

Figure 2 Sensing and controlling the microbiota. (A) The appropriate detection and antigen sampling of the microbiota through many mechanisms results in a healthy host response leading to control of the microbiota. (B) Defective detection of the microbiota and an insufficient host response leads to a loss of control of the microbiota, including the expansion of the total bacteria or specific bacterial populations. DC, dendritic cell; MAMP, microbe associated molecular pattern; IgA, immunoglobulin A; TLR, toll-like receptor; NOD, nucleotide-binding oligomerization domain.

Table 1 Examples of changes in host physiology resulting in changes in the gut microbiota

Component	Function	Findings	Ref
MUC2	Physical barrier	MUC2 deficient mice have bacteria in direct contact with the mucosa leading to inflammation	48
RegIIIγ	Antimicrobial activity	Reduced expression results in the expansion of opportunistic Gram-positive pathogens	62
IgA	Antimicrobial activity	Commensal specific IgG develops in absence of IgA expression	90
MyD88	Microbial detection	MyD88^−/− mice have commensal bacteria in liver and spleen	77
NOD2	Microbial detection	NOD2^−/− mice have reduced bactericidal activity and an expansion in mucosal microbial colonization	70
MHC	Antigen presentation	Bacterial composition and activity varies according to MHC haplotype	87

MUC, mucin; Ig, immunoglobulin; NOD, nucleotide-binding oligomerization domain; MHC, major histocompatibility complex.

Johansson MEV, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc Nat Acad Sci USA 2008; 105:15064 - 15069

 PubMed Web of Science ®Google Scholar

Brandl K, Plitas G, Mihu CN, Ubeda C, Jia T, Fleisher M, et al. Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature 2008; 455:804 - 808

 PubMed Web of Science ®Google Scholar

Macpherson AJ, Gatto D, Sainsbury E, Harriman GR, Hengartner H, Zinkernagel RM. A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 2000; 288:2222 - 2226

 PubMed Web of Science ®Google Scholar

Slack E, Hapfelmeier S, Stecher B, Velykoredko Y, Stoel M, Lawson MAE, et al. Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism. Science 2009; 325:617 - 620

 PubMed Web of Science ®Google Scholar

Meyer-Hoffert U, Hornef MW, Henriques-Normark B, Axelsson LG, Midtvedt T, Putsep K, et al. Secreted enteric antimicrobial activity localises to the mucus surface layer. Gut 2008; 57:764 - 771

 PubMed Web of Science ®Google Scholar

Toivanen P, Vaahtovuo J, Eerola E. Influence of major histocompatibility complex on bacterial composition of fecal flora. Infect Immun 2001; 69:2372 - 2377

 PubMed Web of Science ®Google Scholar