Control of commensal microbiota by the adaptive immune system

Abstract

The symbiotic relationship between the mammalian host and gut microbes has fascinated many researchers in recent years. Use of germ-free animals has contributed to our understanding of how commensal microbes affect the host. Immunodeficiency animals lacking specific components of the mammalian immune system, on the other hand, enable studying of the reciprocal function-how the host controls which microbes to allow for symbiosis. Here we review the recent advances and discuss our perspectives of how to better understand the latter, with an emphasis on the effects of adaptive immunity on the composition and diversity of gut commensal bacteria.

Keywords: AID, activation-induced cytidine deaminase; FISH, fluorescent in situ hybridization; HIV, human immunodeficiency virus; IHC, immunohistochemistry; LN, lymph node; Rag1KO, recombination-activating gene 1-knockout; SFB, segmented filamentous bacteria; adaptive immunity; adoptive transfer; colonization; humanized mice; microbiota; pIgR, polymeric Ig receptor; rRNA.

Figure 1.

Effect of lymphocyte transfer on the gut microbiota. Rag1KO mice were transplanted with either wild-type (n = 6) or Rag1KO (n = 6) bone marrow and analyzed 8 weeks after the transfer. Diversity measured as observed bacterial species and Shannon index is shown. Statistical comparison was based on unpaired t-test (*P < 0.05).

Figure 2.

Adoptive transfer in mice to understand how adaptive immunity controls gut microbiota. (A) Donor mice and cell sorting. Different subsets of mature T and B lymphocytes and progenitors can be sorted from wild-type mice by fluorescence-activated cell sorting (FACS). LN, lymph node. (B) Reconstitution and analyses of recipient mice. Donor cells from either wild-type or immunodeficient mice (e.g., Rag1KO) will be labeled to allow for cell tracking and direct analysis after adoptively transferred into immunodeficient recipient mice. Microbiota samples can be taken from multiple anatomic sites along the gastrointestinal tract, followed by 16S rRNA and metagenomic sequencing analyses. Bacterial taxa that are differentially presented (yellow triangles) will be identified. Donor and recipient mice should be of the same genetic background except for the gene(s) causing immunodeficiency. The two groups of recipient mice should be littermates and housed under specific pathogen-free (not germ-free) conditions.